Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.Epitopes: Sites on an antigen that interact with specific antibodies.Antibodies, Neoplasm: Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.Antibodies, Protozoan: Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Antibodies, Fungal: Immunoglobulins produced in a response to FUNGAL ANTIGENS.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Antibodies, Bispecific: Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Single-Chain Antibodies: A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.Mice, Inbred BALB CAntibodies, Blocking: Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Immunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Antibodies, Heterophile: Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.Antibodies, Catalytic: Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Fluorescent Antibody Technique, Indirect: A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID SYNDROME; related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Antigens: Substances that are recognized by the immune system and induce an immune reaction.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Immunization, Passive: Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Immunoassay: A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.Immunoglobulin Fragments: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.Molecular Weight: The sum of the weight of all the atoms in a molecule.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Hemagglutination Tests: Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)Hemagglutination Inhibition Tests: Serologic tests in which a known quantity of antigen is added to the serum prior to the addition of a red cell suspension. Reaction result is expressed as the smallest amount of antigen which causes complete inhibition of hemagglutination.Antibodies, Antineutrophil Cytoplasmic: Autoantibodies directed against cytoplasmic constituents of POLYMORPHONUCLEAR LEUKOCYTES and/or MONOCYTES. They are used as specific markers for GRANULOMATOSIS WITH POLYANGIITIS and other diseases, though their pathophysiological role is not clear. ANCA are routinely detected by indirect immunofluorescence with three different patterns: c-ANCA (cytoplasmic), p-ANCA (perinuclear), and atypical ANCA.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Seroepidemiologic Studies: EPIDEMIOLOGIC STUDIES based on the detection through serological testing of characteristic change in the serum level of specific ANTIBODIES. Latent subclinical infections and carrier states can thus be detected in addition to clinically overt cases.Immunoglobulin Idiotypes: Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Immunologic Techniques: Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Immunosorbent Techniques: Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.Antibody Diversity: The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Hepatitis C Antibodies: Antibodies to the HEPATITIS C ANTIGENS including antibodies to envelope, core, and non-structural proteins.Isoantibodies: Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.Immunoglobulin Isotypes: The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Hepatitis B Antibodies: Antibodies to the HEPATITIS B ANTIGENS, including antibodies to the surface (Australia) and core of the Dane particle and those to the "e" antigens.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Immunity, Maternally-Acquired: Resistance to a disease-causing agent induced by the introduction of maternal immunity into the fetus by transplacental transfer or into the neonate through colostrum and milk.Insulin Antibodies: Antibodies specific to INSULIN.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Spleen: An encapsulated lymphatic organ through which venous blood filters.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Mice, Inbred C57BLRecombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Serologic Tests: Diagnostic procedures involving immunoglobulin reactions.Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.Single-Domain Antibodies: An immunoglobulin fragment composed of one variable domain from an IMMUNOGLOBULIN HEAVY CHAIN or IMMUNOGLOBULIN LIGHT CHAIN.Polysaccharides, Bacterial: Polysaccharides found in bacteria and in capsules thereof.Kinetics: The rate dynamics in chemical or physical systems.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Bacterial Vaccines: Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Immunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Viral Vaccines: Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Immunoglobulin E: An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).Epitopes, B-Lymphocyte: Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Agglutination Tests: Tests that are dependent on the clumping of cells, microorganisms, or particles when mixed with specific antiserum. (From Stedman, 26th ed)Vaccines, Synthetic: Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Immunotoxins: Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (ANTIBODIES, ANTIPHOSPHOLIPID). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (ANTIBODIES, ANTICARDIOLIPIN). Present also are high levels of lupus anticoagulant (LUPUS COAGULATION INHIBITOR).Radioimmunodetection: Use of radiolabeled antibodies for diagnostic imaging of neoplasms. Antitumor antibodies are labeled with diverse radionuclides including iodine-131, iodine-123, indium-111, or technetium-99m and injected into the patient. Images are obtained by a scintillation camera.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.HIV Envelope Protein gp120: External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.Cell Adhesion: Adherence of cells to surfaces or to other cells.beta 2-Glycoprotein I: A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Immunoglobulin A, Secretory: The principle immunoglobulin in exocrine secretions such as milk, respiratory and intestinal mucin, saliva and tears. The complete molecule (around 400 kD) is composed of two four-chain units of IMMUNOGLOBULIN A, one SECRETORY COMPONENT and one J chain (IMMUNOGLOBULIN J-CHAINS).HemocyaninFluorescent Antibody Technique, Direct: A form of fluorescent antibody technique utilizing a fluorochrome conjugated to an antibody, which is added directly to a tissue or cell suspension for the detection of a specific antigen. (Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Tetanus ToxoidAdjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Bacterial Proteins: Proteins found in any species of bacterium.Goats: Any of numerous agile, hollow-horned RUMINANTS of the genus Capra, in the family Bovidae, closely related to the SHEEP.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Rheumatoid Factor: Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.Immunity, Humoral: Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.Immunization, Secondary: Any immunization following a primary immunization and involving exposure to the same or a closely related antigen.Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of Gram-negative bacteria.Viral Proteins: Proteins found in any species of virus.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Immunoglobulin Fc Fragments: Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Protozoan Proteins: Proteins found in any species of protozoan.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Cell Line, Tumor: A cell line derived from cultured tumor cells.Receptors, Fc: Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Opsonin Proteins: Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.Indium Radioisotopes: Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.Antibody-Producing Cells: Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Staining and Labeling: The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts.Gangliosides: A subclass of ACIDIC GLYCOSPHINGOLIPIDS. They contain one or more sialic acid (N-ACETYLNEURAMINIC ACID) residues. Using the Svennerholm system of abbrevations, gangliosides are designated G for ganglioside, plus subscript M, D, or T for mono-, di-, or trisialo, respectively, the subscript letter being followed by a subscript arabic numeral to indicated sequence of migration in thin-layer chromatograms. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1997)Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Evaluation Studies as Topic: Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.Protein Engineering: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.Hemolytic Plaque Technique: A method to identify and enumerate cells that are synthesizing ANTIBODIES against ANTIGENS or HAPTENS conjugated to sheep RED BLOOD CELLS. The sheep red blood cells surrounding cells secreting antibody are lysed by added COMPLEMENT producing a clear zone of HEMOLYSIS. (From Illustrated Dictionary of Immunology, 3rd ed)Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Radioimmunoprecipitation Assay: Sensitive assay using radiolabeled ANTIGENS to detect specific ANTIBODIES in SERUM. The antigens are allowed to react with the serum and then precipitated using a special reagent such as PROTEIN A sepharose beads. The bound radiolabeled immunoprecipitate is then commonly analyzed by gel electrophoresis.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cattle Diseases: Diseases of domestic cattle of the genus Bos. It includes diseases of cows, yaks, and zebus.Camelids, New World: Ruminant mammals of South America. They are related to camels.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Antigens, CD20: Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.Rubella virus: The type (and only) species of RUBIVIRUS causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.

Post-infection immunodeficiency virus control by neutralizing antibodies. (1/2207)

BACKGROUND: Unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (NAbs), primary HIV infections are not met with such potent and early antibody responses. This brings into question if or how the presence of potent antibodies can contribute to primary HIV control, but protective efficacies of antiviral antibodies in primary HIV infections have remained elusive; and, it has been speculated that even NAb induction could have only a limited suppressive effect on primary HIV replication once infection is established. Here, in an attempt to answer this question, we examined the effect of passive NAb immunization post-infection on primary viral replication in a macaque AIDS model. METHODS AND FINDINGS: The inoculums for passive immunization with simian immunodeficiency virus mac239 (SIVmac239)-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC)-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced T cell priming. CONCLUSIONS: Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for sterile HIV protection by prophylactic vaccination has been suggested, this study points out a possibility of non-sterile HIV control by prophylactic vaccine-induced, sub-sterile titers of NAbs post-infection, providing a rationale of vaccine-based NAb induction for primary HIV control.  (+info)

IgG fc receptors provide an alternative infection route for murine gamma-herpesvirus-68. (2/2207)

BACKGROUND: Herpesviruses can be neutralized in vitro but remain infectious in immune hosts. One difference between these settings is the availability of immunoglobulin Fc receptors. The question therefore arises whether a herpesvirus exposed to apparently neutralizing antibody can still infect Fc receptor(+) cells. PRINCIPAL FINDINGS: Immune sera blocked murine gamma-herpesvirus-68 (MHV-68) infection of fibroblasts, but failed to block and even enhanced its infection of macrophages and dendritic cells. Viral glycoprotein-specific monoclonal antibodies also enhanced infection. MHV-68 appeared to be predominantly latent in macrophages regardless of whether Fc receptors were engaged, but the infection was not abortive and new virus production soon overwhelmed infected cultures. Lytically infected macrophages down-regulated MHC class I-restricted antigen presentation, endocytosis and their response to LPS. CONCLUSIONS: IgG Fc receptors limit the neutralization of gamma-herpesviruses such as MHV-68.  (+info)

The murine gammaherpesvirus-68 gp150 acts as an immunogenic decoy to limit virion neutralization. (3/2207)

Herpesviruses maintain long-term infectivity without marked antigenic variation. They must therefore evade neutralization by other means. Immune sera block murine gammaherpesvirus-68 (MHV-68) infection of fibroblasts, but fail to block and even enhance its infection of IgG Fc receptor-bearing cells, suggesting that the antibody response to infection is actually poor at ablating virion infectivity completely. Here we analyzed this effect further by quantitating the glycoprotein-specific antibody response of MHV-68 carrier mice. Gp150 was much the commonest glycoprotein target and played a predominant role in driving Fc receptor-dependent infection: when gp150-specific antibodies were boosted, Fc receptor-dependent infection increased; and when gp150-specific antibodies were removed, Fc receptor-dependent infection was largely lost. Neither gp150-specific monoclonal antibodies nor gp150-specific polyclonal sera gave significant virion neutralization. Gp150 therefore acts as an immunogenic decoy, distorting the MHV-68-specific antibody response to promote Fc receptor-dependent infection and so compromise virion neutralization. This immune evasion mechanism may be common to many non-essential herpesvirus glycoproteins.  (+info)

Post-exposure vaccination improves gammaherpesvirus neutralization. (4/2207)

Herpesvirus carriers transmit infection despite making virus-specific antibodies. Thus, their antibody responses are not necessarily optimal. An important question for infection control is whether vaccinating carriers might improve virus neutralization. The antibody response to murine gamma-herpesvirus-68 (MHV-68) blocks cell binding, but fails to block and even enhances an IgG Fc receptor-dependent infection of myeloid cells. Viral membrane fusion therefore remains intact. Although gH/gL-specific monoclonal antibodies can block infection at a post-binding step close to membrane fusion, gH/gL is a relatively minor antibody target in virus carriers. We show here that gH/gL-specific antibodies can block both Fc receptor-independent and Fc receptor-dependent infections, and that vaccinating virus carriers with a gH/gL fusion protein improves their capacity for virus neutralization both in vitro and in vivo. This approach has the potential to reduce herpesvirus transmission.  (+info)

Pediatric measles vaccine expressing a dengue antigen induces durable serotype-specific neutralizing antibodies to dengue virus. (5/2207)

Dengue disease is an increasing global health problem that threatens one-third of the world's population. Despite decades of efforts, no licensed vaccine against dengue is available. With the aim to develop an affordable vaccine that could be used in young populations living in tropical areas, we evaluated a new strategy based on the expression of a minimal dengue antigen by a vector derived from pediatric live-attenuated Schwarz measles vaccine (MV). As a proof-of-concept, we inserted into the MV vector a sequence encoding a minimal combined dengue antigen composed of the envelope domain III (EDIII) fused to the ectodomain of the membrane protein (ectoM) from DV serotype-1. Immunization of mice susceptible to MV resulted in a long-term production of DV1 serotype-specific neutralizing antibodies. The presence of ectoM was critical to the immunogenicity of inserted EDIII. The adjuvant capacity of ectoM correlated with its ability to promote the maturation of dendritic cells and the secretion of proinflammatory and antiviral cytokines and chemokines involved in adaptive immunity. The protective efficacy of this vaccine should be studied in non-human primates. A combined measles-dengue vaccine might provide a one-shot approach to immunize children against both diseases where they co-exist.  (+info)

Autocrine semaphorin3A stimulates alpha2 beta1 integrin expression/function in breast tumor cells. (6/2207)

 (+info)

The neutralization of interferons by antibody III. The constant antibody bioassay, a highly sensitive quantitative detector of low antibody levels. (7/2207)

 (+info)

VEGF neutralizing antibody increases the therapeutic efficacy of vinorelbine for renal cell carcinoma. (8/2207)

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*Neutralizing antibody

The difference between neutralizing antibodies and binding antibodies is that neutralizing antibodies neutralize the biological ... A neutralizing antibody (NAb) is an antibody that defends a cell from an antigen or infectious body by neutralizing any effect ... are commonly targeted by neutralizing antibodies. A few examples are Rebif, Betaseron and Avonex. Blocking antibody Mike Recher ... Neutralizing antibodies have shown potential in the treatment of retroviral infections. Medical professionals and researchers ...

*Broadly neutralizing HIV-1 antibodies

... (bNAbs) are neutralizing antibodies which neutralize multiple HIV-1 viral strains. bNAbs ... Database of Broadly Neutralizing HIV-1 Antibodies (bNAbs) LANL Antibody Database. ... database of broadly neutralizing HIV antibodies. Nucleic Acids Research Database issue Volume 42 Issue D1 1 January 2014 PubMed ... Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature, 458, 636. ...

*Scripps Research Institute

"IAVIs Neutralizing Antibody Center". scripps.edu. 6 March 2015. "Pearson Center for Alcoholism and Addiction Research". ... Center for Regenerative Medicine Dorris Neuroscience Center Molecular Screening Center IAVI's Neutralizing Antibody Center at ...

*Barton Haynes

... the isolation of rare broad neutralizing HIV antibodies and their ancestor antibodies; and 8) the development of a new strategy ... He led the group that deciphered the maturation pathways of several types of broadly neutralizing antibodies that point the way ... Host controls of HIV neutralizing antibodies". Science. 344 (6184): 588-589. doi:10.1126/science.1254990. PMC 4162091 . PMID ... the discovery of host tolerance mechanisms that limit the induction of broad neutralizing antibodies in HIV-1 infection; 3) the ...

*Gp41

"HIV broadly neutralizing antibody targets". Current Opinion in HIV and AIDS. 10 (3): 135-143. doi:10.1097/coh.0000000000000153 ... The fusion peptide on the N-terminus of the gp41 is also a potential target because it contains neutralizing antibody epitopes ... "Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody". Science. 352 (6287): 828-833. doi:10.1126/science ... The structure is cage-like with a hollow center that inhibits antibody access. While gp120 sits on the surface of the viral ...

*Ricin

"Human trial proves ricin vaccine safe, induces neutralizing antibodies; further tests planned". University of Texas ... Because ricin is a protein, it can be linked to a monoclonal antibody to target cancerous cells recognized by the antibody. The ... Another antidote developed by the U.S. military has been shown to be safe and effective in lab mice injected with antibody-rich ... probably due to his body's production of antibodies. When a ricin-laced pellet was removed from the small of his back it was ...

*Henipavirus

Both vaccines have been shown[who?] to induce strong neutralizing antibodies in different laboratory animals. Trials began in ... we identified virus replication and generation of neutralizing antibodies, but no clinical disease was observed. As such, this ... Antibodies to Cedar virus were shown to cross react with, but not cross neutralize Hendra or Nipah virus. Despite this close ... On 26 July 2011 a dog living on the Mt Alford property was reported to have HeV antibodies, the first time an animal other than ...

*2015-16 Zika virus epidemic

The PRINT test looks for viral-specific neutralizing antibodies. However, this test can still produce false positive results, ... A test for IgM antibodies has seen to be effective over longer periods of time, as these antibodies can be present starting 4 ... The methods currently available to test for Zika antibodies cross-react with dengue antibodies. An IgM-positive result in a ... However, it is suggested that a PRINT test be performed following a test for IgM antibodies to help eliminate false positives ...

*Psoriasis

Individuals with psoriasis may develop neutralizing antibodies against monoclonal antibodies. Neutralization occurs when an ... The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and ... Neutralizing antibodies have not been reported against etanercept, a biologic drug that is a fusion protein composed of two TNF ... Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α ...

*Mannose

These mannose residues are the target for broadly neutralizing antibodies. Recombinant proteins produced in yeast may be ... "Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies". Nature ... Crispin, Max; Doores, Katie J (2015-04-01). "Targeting host-derived glycans on enveloped viruses for antibody-based vaccine ... "Mannose addition by yeast Pichia Pastoris on recombinant HER-2 protein inhibits recognition by the monoclonal antibody ...

*Canakinumab

... a human monoclonal antibody neutralizing IL-1β". MAbs. 7 (6): 1151-60. doi:10.1080/19420862.2015.1081323. PMC 4966334 . PMID ... Canakinumab (INN, trade name Ilaris, previously ACZ885) is a human monoclonal antibody targeted at interleukin-1 beta. It has ...

*Enterovirus E

Smyth, M. S.; Trudgett, A.; Hoey, E. M.; Martin, S. J.; Brown, F. (1992). "Characterization of neutralizing antibodies to ... "Chemically synthesized peptides elicit neutralizing antibody to bovine enterovirus". The Journal of General Virology. 71 (1): ... Electron microscopy, PCR, complement fixation, antibody fluorescence, neutralization test, and haemagglutination can be used to ...

*Rabies virus

... have been shown to be unable to elicit production of virus neutralizing antibodies. The epitopes which bind neutralizing ... Additionally, a monoclonal antibody with neutralizing functionality has been demonstrated to target antigenic site I. Other ... Upon viral entry into the body and also after vaccination, the body produces virus neutralizing antibodies which bind and ... Apr 2005). "Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: fine mapping and escape mutant ...

*Orungo virus

Tomori O, Fabiyi A (Sep 1976). "Neutralizing antibodies to Orungo virus in man and animals in Nigeria". Tropical and ... Antibodies to the virus have been found in humans, monkeys, sheep, and cattle. "Virus Taxonomy: 2011 Release". International ...

*Bovine papillomavirus

Protection appears to be mediated via type-specific neutralising antibodies. Vaccination of calves as early as 4-6 weeks might ...

*2F5 antibody

2F5 is a broadly neutralizing human monoclonal antibody (mAb) that has been shown to bind to and neutralize HIV-1 in vitro, ... 2F5 is not the only HIV-1-neutralizing antibody found; however, it is the broadest and prevents viral infection when ... A major goal recently in HIV-1 vaccinations is eliciting the broadly neutralizing antibodies before the virus is actually ... Stiegler, G. (2003-04-01). "Therapeutic potential of neutralizing antibodies in the treatment of HIV-1 infection". Journal of ...

*Antonio Lanzavecchia

Neutralizing antibodies were isolated against SARS, cytomegalovirus, avian influenza and dengue virus. Unusually potent ... Human monoclonal antibodies and vaccine design: Taking advantage of his studies on human memory B cells (16), Lanazvecchia ... issues on the role of somatic mutations and the pathways leading to the development of broadly neutralizing antibodies and ... These fully human monoclonal antibodies can be used not only as drugs for prophylaxis and therapy of infectious diseases, but ...

*Cardiolipin

HIV-1 envelope glycoprotein contains at least four sites for neutralizing antibodies. Among these sites, the membrane-proximal ... These antibodies are usually picked up in young women with recurrent spontaneous abortions. In anti-cardiolipin-mediated ... Hokama Y, Campora CE, Hara C, Kuribayashi T, Le Huynh D, Yabusaki K. Anticardiolipin antibodies in the sera of patients with ... Anti-cardiolipin antibodies can also be increased in numerous other conditions, including systemic lupus erythematosus, malaria ...

*Carlumab

"Structural basis for high selectivity of anti-CCL2 neutralizing antibody CNTO 888". Molecular Immunology. 51 (2): 227-233. doi: ... Carlumab (alternate identifier CNTO 888) is a discontinued human recombinant monoclonal antibody (type IgG1 kappa) that targets ... a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors". Cancer Chemotherapy and Pharmacology ... a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer". ...

*Zika fever

Smithburn, K. C.; Kerr, J. A.; Gatne, P. B. (1 April 1954). "Neutralizing antibodies against certain viruses in the sera of ... Later on, serology for the detection of specific IgM and IgG antibodies to Zika virus can be used. IgM antibodies can be ... Surveys have found antibodies to Zika in healthy people in India which could indicate past exposure, though it could also be ... This means that not only can the virus cross the placental barrier, but also the antibodies produced by the mother can reach ...

*Multiple sclerosis drug pipeline

Interferon injections can induce neutralising antibodies against them, turning the medication ineffective. IFN-β 1b is more ... Natalizumab can also induce neutralising antibodies 4 to 6 months after treatment initiation. Fetuin-A (alpha-2-HS-glycoprotein ... Human anti-chimeric antibodies (HACA) appear in patients treated with Rituximab. MTX reduces them. A safety analysis of RA ... other anti-CD20 monoclonal antibody, also in phase II for MS, and phase III for others autoimmune diseases Stem cell ...

*Fresolimumab

"A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions". Proceedings of the National Academy of ... Fresolimumab (GC1008) is a human monoclonal antibody and an immunomodulator. It is intended for the treatment of idiopathic ... Fresolimumab was discovered by Cambridge Antibody Technology (CAT) scientists and was one of a pair of candidate drugs that ...

*Interferon beta-1a

One of the factors related to non-respondance is the presence of high levels of interferon beta neutralizing antibodies. ... Interferon therapy, and specially interferon beta 1b, induces the production of neutralizing antibodies, usually in the second ... Giovannoni G, Munschauer FE, Deisenhammer F (November 2002). "Neutralising antibodies to interferon beta during the treatment ...

*Anakinra

... production of antibodies with neutralizing activity. Blood and blood forming organs : Frequently, decrease in neutrophil counts ... A meeting of experts on Schnitzler's syndrome concluded that "Interleukin-1-neutralizing agents such as anakinra are clearly ...

*DKK1

Neutralizing antibody against DKK-1 reversed DHT effects on outer root sheath keratinocytes. DKK-1 expression is attenuated by ...

*Phage display

"In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden ... Antibody phage display was later used by Carlos F. Barbas at The Scripps Research Institute to create synthetic human antibody ... HUMIRA, an antibody to TNF alpha, was the world's first fully human antibody, which achieved annual sales exceeding $1bn. Below ... The invention of antibody phage display revolutionised antibody drug discovery. Initial work was done by laboratories at the ...
TY - JOUR. T1 - Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers. AU - Chou, Ai Hsiang. AU - Liu, Chia Chyi. AU - Chang, Jui Yuan. AU - Jiang, Renee. AU - Hsieh, Yi Chin. AU - Tsao, Amanda. AU - Wu, Chien Long. AU - Huang, Ju Lan. AU - Fung, Chang Phone. AU - Hsieh, Szu Min. AU - Wang, Ya Fang. AU - Wang, Jen Ren. AU - Hu, Mei Hua. AU - Chiang, Jen Ron. AU - Su, Ih Jen. AU - Chong, Pele Choi Sing. PY - 2013/11/21. Y1 - 2013/11/21. N2 - Background: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac) at 5- and 10-μg doses. In this study we report the cross-neutralizing antibody responses from each ...
Seth, Ankit, Santosh K. Maurya, Ashish Srivastava (2014) Formulation development, characterization and estimation of acid neutralization capacity of shankha bhasma tablets for the treatment of dyspepsia. [Publication] Full text not available from this repository ...
In this study, we established that after 3 years of infection, the frequency of individuals with neutralization breadth in the CAPRISA cohort was 17.5% (7/40 participants). In some individuals, cross-neutralizing antibodies appeared to target subtype-specific determinants, while in others these antibodies were aimed at more universal epitopes. Heterologous neutralizing antibodies first appeared in some individuals as early as 1 year postinfection but peaked at 4 years, with no increases thereafter. The number of viruses neutralized was associated with the viral load and CD4+ T cell count at set point (6 months postinfection) as well as with the drop in CD4+ T cell count between preinfection and 6 months, suggesting that early events in HIV infection set the stage for the development of breadth.. Broadly cross-neutralizing antibodies were produced in a small proportion of individuals within the CAPRISA cohort after 3 years of follow-up. The frequency and extent of neutralization breadth found in ...
4LSS: Crystal structure of broadly and potently neutralizing antibody VRC01 in complex with HIV-1 clade A strain KER_2018_11 gp120
Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. We hypothesize that consistent bnAb elicitation will require germline-targeting priming immunogens, to activate bnAb precursor B cells, and structure-guided, or reductionist, boosting immunogens, to shepherd antibody maturation toward bnAb development. To test this hypothesis, we have focused our initial immunogen design work on VRC01- and PGT121-class bnAbs, but we are addressing other bnAb classes as well, because an effective vaccine will likely need to induce multiple bnAbs of complementary specificities. Our efforts to design, evaluate and optimize the immunogens and immunization regimens are iterative, collaborative and multi-disciplinary. Overall, the work in progress represents an attempt to introduce a new way to design vaccines.. ...
A family of broadly neutralizing antibodies from a chronically infected donor provides a schematic for designing vaccines and treatments that target multiple strains of the virus.. 0 Comments. ...
A family of broadly neutralizing antibodies from a chronically infected donor provides a schematic for designing vaccines and treatments that target multiple strains of the virus.. 0 Comments. ...
Projects:. 1. Nussenzweig. Obtain new human antibodies that neutralize HIV strains resistant to current bNAbs and produce mouse models to examine how B cells producing bNAbs develop from their progenitors in vivo.. 2. Ravetch. Investigate the contributions of Fc effector function to the newly-isolated HIV bNAbs in vitro and in a new in vivo mouse model for HIV entry.. 3. Bjorkman. Determine the structural correlates of broad and potent neutralization and improved effector functions. ...
Atomic structure of the antibody VRC01 (blue and green) binding to HIV (grey and red). The precise site of VRC01-HIV binding (red) is a subset of the area ...
4OLZ: Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo.
Rabbit polyclonal Bid Cleavage Site antibody validated for WB and tested in Human and Mouse. Referenced in 2 publications and 1 independent review. Immunogen…
The membrane proximal external region (MPER) of the gp41 subunit of the HIV-1 envelope glycoprotein (Env) contains determinants for broadly neutralizing antibodies and has remained an important focus of vaccine design. However, creating an immunogen that elicits broadly neutralizing antibodies to this region has proven difficult in part due to the relative inaccessibility of the MPER in the native conformation of Env. Here, we describe the antigenicity and immunogenicity of a panel of oligomeric gp41 immunogens designed to model a fusion-intermediate conformation of Env in order to enhance MPER exposure in a relevant conformation. The immunogens contain segments of the gp41 N- and C-heptad repeats to mimic a trapped intermediate, followed by the MPER, with variations that include different N-heptad lengths, insertion of extra epitopes, and varying C-termini. These well-characterized immunogens were evaluated in two different immunization protocols involving gp41 and gp140 proteins, gp41 and gp160 DNA
Failure to elicit broadly neutralizing (bNt) antibodies (Abs) against the membrane-proximal external region of HIV-1 gp41 (MPER) reflects the difficulty of mimicking its neutralization-competent structure (NCS). Here, we analyzed MPER antigenicity in the context of the plasma membrane and identified a role for the gp41 transmembrane domain (TM) in exposing the epitopes of three bNt monoclonal Abs (MAbs) (2F5, 4E10, and Z13e1). We transiently expressed DNA constructs encoding gp41 ectodomain fragments fused to either the TM of the platelet-derived growth factor receptor (PDGFR) or the gp41 TM and cytoplasmic tail domain (CT). Constructs encoding the MPER tethered to the gp41 TM followed by a 27-residue CT fragment (MPER-TM1) produced optimal MAb binding. Critical binding residues for the three Nt MAbs were identified using a panel of 24 MPER-TM1 mutants bearing single amino acid substitutions in the MPER; many were previously shown to affect MAb-mediated viral neutralization. Moreover, non-Nt ...
An understanding of how broadly neutralizing activity develops in HIV-1-infected individuals is needed to guide vaccine design and immunization strategies. Here we used a large panel of 44 HIV-1 envelope variants (subtypes A, B, and C) to evaluate the presence of broadly neutralizing antibodies in serum samples obtained 3 years after seroconversion from 40 women enrolled in the CAPRISA 002 acute infection cohort. Seven of 40 participants had serum antibodies that neutralized more than 40% of viruses tested and were considered to have neutralization breadth. Among the samples with breadth, CAP257 serum neutralized 82% (36/44 variants) of the panel, while CAP256 serum neutralized 77% (33/43 variants) of the panel. Analysis of longitudinal samples showed that breadth developed gradually starting from year 2, with the number of viruses neutralized as well as the antibody titer increasing over time. Interestingly, neutralization breadth peaked at 4 years postinfection, with no increase thereafter. ...
In this study, the identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and the gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of ...
The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone ...
The elicitation and generation of a particular antibody response requires at least three steps: antibody gene recombination to form naive B-cell receptors, deletion of autoreactive B-cell clones, and antigen-driven affinity maturation of the antibody response. Surprisingly, despite the presence of substantial quantities of gp120 in HIV-1 infected individuals, the human immune system often does not make antibodies against the CD4-binding site that are effective at neutralizing primary isolates of HIV-1. When CD4-binding site directed neutralizing antibodies do arise, it is only after several years of ongoing HIV-1 infection [20,30]. The reasons for the poor immune response to this important region of HIV-1 Env are unknown. We have analysed the maturation of the antibody VRC01 as a way to provide insight into which of these steps might be responsible for the reduced elicitation of potent CD4-binding site antibodies and perhaps high-affinity neutralizing antibodies in general [25].. Our ...
In the past few years, several highly potent, broadly neutralizing antibodies (bNAbs) specific for the gp120 envelope protein of HIV-1 have been discovered. The goal of this work is to use this information to inform the design of vaccines that are able to induce such antibodies (see the Perspective by Crowe). However, because of extensive somatic hypermutation, the epitope bound by these antibodies often does not bind to the germline sequence. Jardine et al. (p. 711, published online 28 March; see the cover) used computational analysis and in vitro screening to design an immunogen that could bind to VRC01-class bNAbs and to their germline precursors. Georgiev et al. (p. 751) took advantage of the fact that only four sites on the HIV viral envelope protein seem to bind bNAbs, and sera that contain particular bNAbs show characteristic patterns of neutralization. An algorithm was developed that could successfully delineate the neutralization specificity of antibodies present in polyclonal sera from ...
HIV-neutralizing monoclonal antibodies powerpoint presentation slides is available for free download uploaded in belonging ppt presentation Health & Wellness category, Download and Use!
In this animation, professor Cameron Abrams describes a new molecule that hes developed here at Drexel, called DAVEI. DAVEI essentially neutralizes HIV, by tricking the virus into think that its attached to a cell. The virus then spews out its contents, which float off into oblivion, rendering he virus inert.. "We hypothesized that an important role of the fusion machinery is to open the viral membrane when triggered, and it follows that a trigger didnt necessarily have to be a doomed cell," Abrams said. "So we envisioned particular ways the components of the viral fusion machinery work and designed a molecule that would trigger it prematurely," Abrams said.. The team designed DAVEI from two main ingredients. One piece, called the Membrane Proximal External Region (MPER), is itself a small piece of the fusion machinery and interacts strongly with viral membranes. The other piece, called cyanovirin, binds to the sugar coating of the protein spike. Working together, the MPER and cyanovirin in ...
Rusert, P; Krarup, A; Magnus, C; Brandenberg, O F; Weber, J; Ehlert, A K; Regoes, R R; Günthard, H F; Trkola, A (2011). Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies. Journal of Experimental Medicine, 208(7):1419-1433.. Ruprecht, C R; Krarup, A; Reynell, L; Mann, A M; Brandenberg, O F; Berlinger, L; Abela, I A; Regoes, R R; Günthard, H F; Rusert, P; Trkola, A (2011). MPER-specific antibodies induce gp120 shedding and irreversibly neutralize HIV-1. Journal of Experimental Medicine, 208(3):439-454.. Pugach, P; Krarup, A; Gettie, A; Kuroda, M; Blanchard, J; Piatak Jr, M; Lifson, J D; Trkola, A; Robbiani, M (2010). In vivo binding and retention of CD4-specific DARPin 57.2 in macaques. PLoS ONE, 5(8):e12455.. ...
Researchers have traced in detail how certain powerful HIV neutralizing antibodies evolve, a finding that generates vital clues to guide the design of a preventive HIV vaccine, according
M. Pancera, S. Shahzad-ul-Hussan, N. A. Doria-Rose, K. Dai, J. S. McLellan, R. P. Staupe, Y. Yang, B. Zhang, S. Loesgen, M. N. Amin, L.-X. Wang, D. R. Burton, W. C. Koff, G. J. Nabel, J. R. Mascola, C. A. Bewley, P. D. Kwong: Structure of broadly neutralizing antibody PG16 in complex with HIV-1 gp120 V1/V2 domain reveals complex-type N-glycan recognition. Nat. Struct. Mol. Biol. 2013, 20, 804-813 ...
The neutralization process happens when an acid and a base interact with each other, causing each of the compounds to lose some of their ions and as a result the remaining solution becomes neither an...
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In this study, we attempted to induce mutations in the MN strain of HIV-1 by subjecting the virus to the immunological selective pressure associated with growth in the presence of human serum with high NA activity directed predominately against the V3 region neutralization determinant. We hypothesized that this selective pressure would result in a mutation(s) in the V3 neutralization determinant itself and that the mutation(s) would result in selective resistance to neutralization by the serum used for the selection process and other sera that reacted selectively with the MN V3 neutralization determinant. The four different NR viruses so derived were found to be broadly resistant to neutralization by all of the human sera that we tested, including some that had NA activity that could not be demonstrated to be directed against the V3 determinant by peptide blocking experiments. Sequencing of the PCR DNA spanning the V3 regions of the four different NR viruses derived by this procedure did not ...
Membrane fusion induced by the envelope glycoprotein enables the intracellular replication of HIV-1; hence, this process constitutes a major target for antiretroviral compounds. It has been proposed that peptides having propensity to interact with membrane interfaces might exert broad antiviral activity against enveloped viruses. To test this hypothesis, in this contribution we have analyzed the antiviral effects of peptides derived from the membrane-proximal external region and the transmembrane domain of the envelope glycoprotein subunit gp41, which display different degrees of interfacial hydrophobicity. Our data support the virucidal activity of a region that combines hydrophobic-at-interface membrane-proximal external region aromatics with hydrophobic residues of the transmembrane domain, and contains the absolutely conserved 679LWYIK/R683 sequence, proposed to embody a cholesterol recognition/interaction amino acid consensus motif. We further sought to correlate the antiviral activity ...
The isolation of J3 represents a significant improvement on previous nAbs derived from immunized animals as in single-domain VHH form it has a comparable breadth and potency to the best nAbs obtained from a limited number of natural human infections. In contrast, previous nAb clones characterized from immunized animals have only exhibited limited breadth (Forsman et al., 2008; Sundling et al., 2010). A caveat to this is the observation that sera with 17b-like binding specificity can be induced after immunization of humans (Vaine et al., 2010), and it should be noted that 17b and other Abs to CD4-induced epitopes are less broadly neutralizing as full-length mAbs than in Fab form (Labrijn et al., 2003). However, given the previously reported decrease in neutralization ability seen with the Fab of b12 (Labrijn et al., 2003), it appears the CD4-binding site of Env is not per se more easily targeted for neutralization by small Ab fragments as is the CD4-induced binding site, presumably because of the ...
Advances in technology-especially single-cell antibody cloning techniques-have led to the isolation and characterization of antibodies from people with HIV infection that can neutralize many variants (1). These are referred to as broadly neutralizing antibodies (bnAbs). Such antibodies can be detected in about 25% of persons with untreated HIV-1 infection (2), reflecting a host immune response to unremitting viral replication, generation of large numbers of viral variants, and shifting antigen exposure (3). Although bnAbs may exert some selective pressure as they develop, they generally do not reduce viral burden, improve health, or slow the progression of disease (4). However, they offer considerable opportunities for treatment and prevention of HIV-1 infection in others. At this time, hundreds of bnAbs have been identified; those that have attracted the most attention are bnAbs with the greatest breadth, neutralizing the largest number of HIV-1 strains, including those traditionally most ...
Gli anticorpi neutralizzanti HIV-1 (bNAbs o Broadly Neutralizing HIV-1 Antibodies) sono anticorpi che neutralizzano multipli HIV-1 ceppi virali. Al contrario i non bNAbs sono specifici per i singoli ceppi virali. La scoperta di bNAbs ha portato ad un importante settore della ricerca, vale a dire, la scoperta di un vaccino, non solo limitato a HIV, ma anche altri virus in rapida mutazione come linfluenza et ect. Gli anticorpi neutralizzanti legano regioni conservate delle proteine di superficie del virus. La generazione di un ampio spettro di anticorpi neutralizzanti anti-HIV è un obiettivo nel disegno di vaccino contro lHIV. Leffetto neutralizzante dipende sia dal legame dei bNAbs sulle proteine virali che dallefficiente legame delle bNAbs al recettore Fc. Lefficiente legame con il FcRn (isoforma del recettore Fc) che si verifica sia in vagina che nel retto può migliorare la neutralizzazione nelle porte dingresso naturali del virus HIV. Gli bNAbs possono essere classificati secondo il ...
A protective vaccine against HIV will likely require elicitation of broadly neutralizing antibodies that neutralize a diverse array of HIV strains. Four broadly-neutralizing antibodies are known at present, each targeting a different conserved epitope on the virus. In this project, we focus on the broadly-neutralizing antibody 2F5 that targets an epitope in the membrane-proximal external region of HIV gp41. The project focuses on design of immunogens to re-elicit 2F5-like neutralizing responses, and on redesign of 2F5 itself to improve our understanding of its mechanism of neutralization. Both aims will employ a combination of computational design and directed evolution.. Aim 1: Develop novel membrane-protein based immunogens that conformationally stabilize the 2F5 epitope in the context of a lipid membrane to best approximate the epitope environment on the virion.. Aim 2: Design and characterize variants of the 2F5 antibody to determine the importance of the length and composition of the ...
Extensive shielding by N-glycans on the surface of the HIV envelope glycoproteins (Env) restricts B cell recognition of conserved neutralizing determinants. Elicitation of broadly neutralizing antibodies (bNAbs) in selected HIV-infected individuals reveals that Abs capable of penetrating the glycan shield can be generated by the B cell repertoire. Accordingly, we sought to determine if targeted N-glycan deletion might alter antibody responses to Env. We focused on the conserved CD4 binding site (CD4bs) since this is a known neutralizing determinant that is devoid of glycosylation to allow CD4 receptor engagement, but is ringed by surrounding N-glycans. We selectively deleted potential N-glycan sites (PNGS) proximal to the CD4bs on well-ordered clade C 16055 native flexibly linked (NFL) trimers to potentially increase recognition by naïve B cells in vivo. We generated glycan-deleted trimer variants that maintained native-like conformation and stability. Using a panel of CD4bs-directed bNAbs, we ...
A new study has shown that infusion of a broadly neutralizing antibody VRC01 in virally suppressed, early treated volunteers was associated with a modestly delayed rebound of HIV after interruption of antiretroviral therapy.
Significant efforts have been made to identify HIV-1 neutralizing antibodies because they are considered to be critical to the design of an effective HIV-1 vaccine. proteins. Keywords: HIV-1, Surface-expressed envelope trimer, Single B cell sort, HIV-1 neutralizing Antibodies 1 Introduction Broadly neutralizing antibodies (bNAbs) targeting HIV-1 can prevent infection in non-human primates, and control HIV-1 replication in humanized mice (Mascola et al., 2000; Hessell et al., 2009; Klein et al., 2012b). These antibodies are therefore of significant interest for vaccine design and as agents for novel therapeutic approaches (McCoy and Weiss, 2013). Given their potential importance, substantial efforts have been made to dissect the human anti-HIV-1 antibody response in individuals who display broad and potent HIV-1 serum neutralizing activity (McCoy and Weiss, 2013). An essential component to this effort has been the development of new methods for antibody cloning from single B cells (Wardemann et ...
Significant efforts have been made to identify HIV-1 neutralizing antibodies because they are considered to be critical to the design of an effective HIV-1 vaccine. proteins. Keywords: HIV-1, Surface-expressed envelope trimer, Single B cell sort, HIV-1 neutralizing Antibodies 1 Introduction Broadly neutralizing antibodies (bNAbs) targeting HIV-1 can prevent infection in non-human primates, and control HIV-1 replication in humanized mice (Mascola et al., 2000; Hessell et al., 2009; Klein et al., 2012b). These antibodies are therefore of significant interest for vaccine design and as agents for novel therapeutic approaches (McCoy and Weiss, 2013). Given their potential importance, substantial efforts have been made to dissect the human anti-HIV-1 antibody response in individuals who display broad and potent HIV-1 serum neutralizing activity (McCoy and Weiss, 2013). An essential component to this effort has been the development of new methods for antibody cloning from single B cells (Wardemann et ...
Researchers at The Scripps Research Institute have uncovered the surprising details of how a powerful anti-HIV antibody grabs hold of the virus.
It has been reported that, during chronic infection, potent and cross-reactive bNAbs that are capable of neutralizing heterologous viruses of diverse subtypes develop in a small portion of HIV-1 infected individuals [28-31]. The effective humoral responses are slow, with NAbs to the initial viral strain appearing after ~12 weeks, and broad NAbs (in 10-30% of individuals) after 2-4 years [30, 32-34]. The development of bNAbs was shown to correlate with high plasma viremia and could result from evolving antigen exposure over many years that has allowed sufficient somatic hypermutation in the B-cell receptors (BCRs) and focuses the B-cell response to the conserved neutralization sites on Env [30]. Therefore, delayed bNAb response might be attributed to the slow, antigen-dependent affinity maturation process. Abs typically accumulate mutations in the complementarity determining region (CDR) loops, i.e. the typical antigen contact region [35]. Whereas most human Abs that have undergone affinity ...
The International AIDS Vaccine Initiative (IAVI) is a global not-for-profit organization whose mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world.
Results IgGs from 10 (19%) patients were able to neutralise HCVpp from ,4/6 subgenotypes tested (bNAb group). Heat-map analysis of competition with antibodies to known domains showed that IgGs from the bNAb group competed with multiple epitopes of E2 (rather than a single region).. HCV viral load was significantly lower in those with broad ELISA binding (p = 0.036). The bNAb group had significantly lower median liver fibrosis (Fibroscan®) readings than those neutralising ,3 subgenotypes (p = 0.046). In the subgroup of 21 patients tested for neutralising ability against a gt 1 panel, individuals clustered into 9 broad, 7 moderate and 5 weak neutralisers on heat-map analysis. Broad neutralising profile was associated with lower levels of liver cirrhosis (p = 0.007). Broad intragenotypic neutralisation status was also associated with AA/AG at SNP rs9275224 in the HLA-DQB1 gene but there was no association with IL28B genotype. ...
The group is dedicated to the development and preclinical as well as clinical testing of HIV candidate vaccines. According to the necessity of rational vaccine design the group is focussing on various aspects of epidemiology, viral pathogenisis and morphogenisis, HIV replication and vaccine manufacturing including preclinical and clinical monitoring of virus specific B- and T-cell responses.
Julien J-P, Lee J H, Cupo A, Murin CD, Derking R, Hoffenberg S, Caulfield MJ, King RC, Marozsan AJ, Klasse P J et al.. 2013. Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9.. Proc Natl Acad Sci U S A. 110(11):4351-6. ...
The Siemens test laboratory for transformer can analyze the neutralization value (acidity), so that timely counteractive measures can be initiated.
Coronary heart disease (CHD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. These arteries supply oxygen-rich blood to your heart muscle. If the flow of oxygen-rich blood to your heart muscle is reduced or blocked, heart attack can occur.. The most common symptom of coronary artery disease is angina, or chest pain. Angina can be described as a discomfort, heaviness, pressure, aching, burning, fullness, squeezing, or painful feeling in your chest. It can be mistaken for indigestion or heartburn. Angina may also be felt in the shoulders, arms, neck, throat, jaw, or back. Other symptoms of coronary artery disease include:. ...
The H7N9 viruses have been circulating for six years. The insertion of a polybasic cleavage site in the haemagglutinin (HA) protein of H7N9 has resulted in the emergence of a highly pathogenic (HP) avian influenza virus. Currently, there are limited studies on neutralizing monoclonal antibodies(mAbs) against HP H7N9 AIVs. In this study, mice were immunized with inactivated H7N9 vaccine of A/ZJU01/PR8/2013 to produce murine mAbs. Finally, two murine mAbs against the HA of low pathogenic (LP) virus were produced and characterized. Characterization included determining mAbs binding breadth and affinity, in vitro neutralization capacity, and potential in vivo protection. Two of these mAbs, 1H10 and 2D1, have been identified to have therapeutic and prophylactic efficacy against the HP strain in mouse passive transfer-viral challenge experiments. The mAb 1H10 was most efficacious, even if the treatment-time was as late as 72 h post-infection, or the therapeutic dose was as low as 1 mg/kg; and it was ...
The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity. ...
A team of NIH scientists has developed a new tool to identify broadly neutralizing antibodies (bNAbs) capable of preventing infection by the majority of HIV strains found around the globe, an advance that could help speed HIV vaccine research. Scientists have long studied HIV-infected individuals whose blood shows powerful neutralization activity because understanding how HIV bNAbs develop and attack the virus can yield clues for HIV vaccine design. But until now, available methods for analyzing blood samples did not easily yield specific information about the HIV bNAbs present or the parts of the virus they targeted. In addition, determining where and how HIV bNAbs bind to the virus has been a laborious process involving several complicated techniques and relatively large quantities of blood from individual donors ...
The high overall genetic homology between humans and rhesus macaques, coupled with the phenotypic conservation of lymphocyte populations, highlights the potential use of nonhuman primates (NHPs) for the preclinical evaluation of vaccine candidates. For HIV-1, experimental models are needed to identify vaccine regimens capable of eliciting desired immune responses, such as broadly neutralizing antibodies (bNAbs). One important neutralization target on the HIV-1 envelope glycoproteins (Envs) is the conserved primary CD4 receptor binding site (CD4bs). The isolation and characterization of CD4bs-specific neutralizing monoclonal Abs (mAbs) from HIV-1-infected individuals have provided insights into how broadly reactive Abs target this conserved epitope. In contrast, and for reasons that are not understood, current Env immunogens elicit CD4bs-directed Abs with limited neutralization breadth. To facilitate the use of the NHP model to address this and other questions relevant to human humoral immunity, ...
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Proteins called broadly neutralizing antibodies (bNAbs) are a promising key to the prevention of infection by HIV, the virus that causes AIDS. bNAbs have been found in blood samples from some HIV patients whose immune systems can naturally control the infection. These antibodies may protect a patients healthy cells by recognizing a protein called the envelope spike, present on the surface of all HIV strains and inhibiting, or neutralizing, the effects of the virus. Now Caltech researchers have discovered that one particular bNAb may be able to recognize this signature protein, even as it takes on different conformations during infection-making it easier to detect and neutralize the viruses in an infected patient.. The work, from the laboratory of Pamela Bjorkman, Centennial Professor of Biology, was published in the September 10 issue of the journal Cell.. The process of HIV infection begins when the virus comes into contact with human immune cells called T cells that carry a particular ...
The HIV virus remains maddeningly clever in eluding vaccines, but there are signs of progress. A post-study analysis of the Thai RV144 vaccine trial found ...
Original citation: J Clin Invest. 2017;127(7):2705-2718. https://doi.org/10.1172/JCI92335. Citation for this corrigendum: J Clin Invest. 2017;127(9):3557. https://doi.org/10.1172/JCI96860. The last two sentences in the first paragraph of the Discussion section were incorrect. The correct sentences are below.. Recently described "ImmTAC" molecules use a TCR-based recognition domain offering similar reactivity to TCRm Abs and demonstrate high affinity (42). Also, TCRm Abs such as Pr20 can target these "undruggable" proteins with high affinity for redirected immune-mediated cytolysis.. The authors regret the error.. ...
Gene therapy, an approach most commonly explored for curing chronic genetic diseases such as cystic fibrosis, may also prove practical for disease prevention. In research published today in Nature1, scientists in California show that a single injection - which inserted the DNA for an HIV-neutralizing antibody into the muscle cells of live mice - completely…
Vical Incorporated (Nasdaq VICL) announced today that the company s Vaxfectin adjuvant has significantly boosted the immune response of DNA-based vaccines again
Mouse monoclonal SFPQ antibody [B92] validated for WB, IP, RIA, IHC, ICC, ICC/IF and tested in Human and Mouse. Referenced in 11 publications and 2 independent…
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Citation. Henry Dunand CJ, Leon PE, Huang M, Choi A, Chromikova V, Ho IY, Tan GS, Cruz J, Hirsh A, Zheng NY, Mullarkey CE, Ennis FA, Terajima M, Treanor JJ, Topham DJ, Subbarao K, Palese P, Krammer F, Wilson PC. Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection.. Cell Host & Microbe. 2016 Jun 08; 19. : 800-13.. External Citation. Abstract. Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic ...
Science, 342(6165), 1477-1483. Julien, J. , Taneva, S. , Nieva, J. , et al. (2010). Ablation of the complementarity-determining region H3 apex of the antiHIV-1 broadly neutralizing antibody 2F5 abrogates neutralizing capacity without affecting core epitope binding. Journal of Virology, 84(9), 4136-4147. , et al. (2012). Targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus. PLoS One, 7(5), e38068. , Matyas, G. , McCutchan, F. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature, 491(7424), 406-412. , et al. (2012). Recognition of membrane-bound fusion-peptide/MPER complexes by the HIV-1 neutralizing 2F5 antibody: Implications for anti-2F5 immunogenicity. PLoS One, 7(12), e52740. , Valpuesta, J. , et al. (2008). The broadly neutralizing anti-human immunodeficiency virus type 1 4E10 monoclonal antibody is better adapted to membrane-bound epitope recognition and blocking than 2F5. Journal of ...
Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of antigen-specific immune responses in controlling plasma viremia in SIV infected rhesus macaques. Thirteen rhesus macaques were inoculated either intravaginally or intrarectally with SIVMAC251. Peripheral blood CD4+ T-cells were quantified. Plasma was examined for viremia, antigen specific IgG, IgA and IgM binding responses and neutralizing antibodies. Regions containing binding epitopes for antigen-specific IgG, IgM and IgA responses were determined, and the minimum size of linear Envelope epitope responsible for binding antibodies was identified. The presence of neutralizing antibodies did not correlate the outcome of the disease. In a few SIV-infected macaques, antigen-specific IgG and IgM responses in plasma
Author Summary An effective HIV vaccine should elicit broadly neutralizing antibodies, i.e. antibodies that neutralize a wide spectrum of different HIVs in vitro. A number of human monoclonal antibodies have been isolated with broad neutralization and shown to protect macaques against vaginal HIV challenge. Protection is generally correlated with neutralization and requires relatively high antibody concentrations that may be difficult to achieve by vaccination. Here, we show that one monoclonal antibody (2G12) is unusually potent in protection relative to its neutralizing ability as hinted at by earlier data. Further studies eliminate an unusual ability of 2G12 to be transported to the vagina (site of infection) as a possible explanation for our observations. Although the precise mechanism is unclear, the studies have important implications for HIV vaccine design in general by suggesting that some vaccine targets on HIV may be better than others and, specifically, by suggesting that the sugar coat of
Antibodies are proteins of the immune system that travel through the bloodstream and recognize potential threats to the body, whether bacteria, viruses or abnormal cells. Most antibodies have a characteristic Y shape. The tips of the Y form a "lock" that binds to a specific "key" carried by foreign bodies that the immune system should destroy.. According to Curiel, recent work by other groups has identified an unusually small and stable class of antibodies made by camels, alpacas and related species collectively classified as camelids. The "lock" of camelid antibodies consists of the stem of the Y only, so it cant unfold in the harsh internal environment of the cell.. "We found that when we incorporated the camelid antibodies into the virus, they retained their binding specificity," Curiel said. "This opens the door to targeting these antibodies to specific tumor markers.". Currently available viral-based cancer therapeutics and those in human trials are not targeted directly to tumor cells. ...
Scientists have isolated the most powerful broadly neutralizing antibodies (bNAbs) against HIV so far - a major step towards finding an effective vaccine against the deadly virus. Capable of fighting a broad spectrum of variants of HIV, the virus that causes AIDS, some of the 17 antibodies discovered jointly by The International AIDS Vaccine Initiative (IAVI) and The Scripps Research Institute blocked HIV infection of cells as much as 10 to 100 times as potently as the previously discovered bNAbs. These HIV neutralizing antibodies are produced naturally by a minority infected with HIV, but who show no symptoms ...
According to a recent study, observing the evolution of a particular type of antibody in an infected HIV-1 patient has provided insights that will enable vaccination strategies that mimic the actual antibody development within the body.
DESCRIPTION (provided by applicant): 4E10 is a monoclonal antibody that was derived from the B cells of a patient with persistent HIV infections. In vitro and in vivo, 4E10 neutralizes a wide variety of HIV and SHIV strains. As such, an immunogen that elicits 4E10-like antibody responses in humans would be a huge advance toward the goal of designing a safe and effective vaccine against HIV. Although the epitope for 4E10 was found to be a six amino acid peptide (NWFNIT) from the fusogenic domain of gp41, attempts to use this peptide as an immunogen to elicit antibodies that mimic the HIV neutralizing activity of 4E10 have been totally unsuccessful. This result indicates that antigen presentation is possibly the missing link that lies between immunization with NWFNIT-containing immunogens and the successful elicitation of 4E10-like antibodies in vivo. For over a decade we have been developing methods in peptide chemistry to induce linear synthetic peptides to assume new conformations. The ...
Looking for neutralization test? Find out information about neutralization test. 1 1. a series of questions or problems designed to test a specific skill or knowledge 2. a. a chemical reaction or physical procedure for testing a... Explanation of neutralization test
Researchers from the Perelman School of Medicine at the University of Pennsylvania have figured out how to make a much-improved research tool that they hope will open the door to new and better HIV vaccine designs.
The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies. Devin Sok*, Uri Laserson*, Jonathan Laserson*, Yi Liu*, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M Walker, Birgitte B Simen, Elizabeth P St John, Po-Ying Chan-Hui, Kristine Swiderek, Stephen H Kleinstein, Galit Alter, Michael S Seaman, Arup K Chakraborty, Daphne Koller, Ian A Wilson, George M Church, Dennis R Burton, Pascal Poignard. PLoS Pathogens 2013. doi:10.1371/journal.ppat.1003754 , pdf. ...
The broad HIV-1 genetic diversity and the emergence of drug resistant variants in Cameroon adds to complicate the viral genetic diversity and poses potential pr...
Researchers report a breakthrough in generating powerful antibodies that can neutralize HIV. An HIV infection is really an intensive molecular arms race launched from the minute the virus infects a new host. AIDS progresses not because the body isnt capable of fighting off HIV - it is.
Looking for neutralization? Find out information about neutralization. chemical reaction, according to the Arrhenius theory of acids and bases acids and bases, two related classes of chemicals; the members of each class have a... Explanation of neutralization
Wong, S.S. and Abd-Jamil, J. and AbuBakar, Sazaly (2007) Antibody neutralization and viral virulence in recurring dengue virus type 2 outbreaks. Viral Immunology, 20 (3). pp. 359-367. ISSN 0882-8245 ...
GenScriptRabbitAnti-PLCγ1(Ab-771)PolyclonalAntibodydetectsendogenouslevelsoftotalPLCγ1protein.FullNamePLCγ1Antibody(Ab-771),pAb,Rabbitabbreviated_name1PLC-γ1(Ab-771)AntibodyIgS
Biomol offers Reagents for Biomedical Research like Antibodies, Assays, Biochemicals, Proteins, Inhibitors and Substrates, Labeling Dyes and more ...
Giving monkeys two powerful anti-HIV antibodies immediately after infection with an HIV-like virus enabled the immune systems of some of the animals to ...
Part 8 of Berry Berry Easy notes on Acids and Bases for Form 4 SPM Chemistry students regarding applications of neutralisation reactions in daily life
The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC50). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such ...
I thought the HPV vaccine Cervarix would protect me against cervical cancer. I thought I would be armed for life. It only took one injection to find out I was wrong.. My regular week used to consist of a 9-5 work schedule, 2-hour workouts at the gym, 10-kilometer runs during weekdays, long-distance runs on the weekends, and a lot of nights out with out-of-town trips with friends in between.. But all that changed when I decided to have my first shot of Cervarix last September 2013.. Our office was offering Cervarix shots at a subsidized price as part of their Health & Wellness program. Since Cervarix shots are sold at an expensive price here in the Philippines, most of us decided to take advantage of the offer.. The day I got my first shot, my arm hurt a lot but I was told that it was just normal and that the pain would go away after a few days. After around 4 days, the pain did go away and I thought that was the last inconvenience Ill experience because of Cervarix.. But I was wrong.. Less ...
A human immunodeficiency virus type 2 (HIV-2)-infected woman experienced asymptomatic superinfection with HIV-1 subtype AG. She did not have cross-neutralizing autologous HIV-1 antibodies before and shortly after HIV-1 superinfection. This evidence supports a mechanism other than cross-neutralizing antibodies for the mild course of HIV-1 infection in this woman.. ...
To evaluate the safety of HIV-1 gp120 C4-V3 hybrid polyvalent peptide immunogen (C4-V3 peptides) formulated in mineral oil containing mannose mono-oleate (IFA) in HIV-1 uninfected volunteers. To evaluate the humoral and cellular immune responses to the C4-V3 peptides as measured by the induction of 1 or more of the following: neutralizing antibodies to HIV-1 MN and RF, cross-neutralizing antibodies to primary isolates of HIV-1, HIV-1 antigen-specific lymphoproliferation, CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity specific for HIV-1 gp120 or V3 peptides corresponding to the vaccine strains of HIV-1, induction of HLA-B7 and HLA-A2 restricted CD8+CTLs, and induction of HIV-specific DTH responses.. The test immunogen (C4-V3 peptides) is constructed from 4 sequences of the HIV-1 V3 gp120 loop shared by approximately 80% of North American HIV-1 strains. Because of the critical role that this region plays in generating anti-HIV sequences, it is hypothesized that the test immunogen (C4-V3 ...
Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific;
Twenty-five monoclonal antibodies were generated by immunizing mice. Of these, the one named R10 had the strongest neutralizing activity against HAV [a 50% neutralizing concentration (neut50) value of ∼2 nM, ∼0.3 μg/mL]. The Fab fragment is also strongly neutralizing (neut50 = ∼3 nM, ∼0.45 μg/mL) (Fig. 1A). R10 does not recognize linear epitopes by immunoblot, but recognizes conformational epitopes by ELISA, and shows similar binding affinities to full and empty particles (Fig. 1B). Interestingly, a fluorescent assay revealed that whereas the R10 Fab portion destabilizes full HAV particles by 7 °C, the intact R10 stabilizes the particles by 2 °C (Fig. 1C and Fig. S1A). The same assay indicates that the bivalent intact antibody induces a two-stage transition in protein conformation to release the RNA genome (Fig. 1C and Fig. S1A). The first event, producing a slight exposure of RNA, occurs at a similar temperature to that seen with the Fab, whereas the second, which fully exposes the ...
An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.
2012 National Academy of Sciences. Freely available online through the PNAS open access option. Contributed by Pamela J. Bjorkman, October 4, 2012 (sent for review September 15, 2012). Published online before print October 30, 2012. Author contributions: H.M and M.C.N conceived the project; H.M., L.S., Z.E., Y.L., H.S., T.F., M.C.N., and P.J.B. designed research; H.M., L.S., Z.E., Y.L., H.S., T.F., M.C.N., and P.J.B. performed research; H.M. produced the antibodies and the HIV Env proteins; H.M. performed and analyzed antibody-binding experiments; L.S. determined and interpreted crystal structures; C.E., J.F.S., and A.H.-S. contributed new reagents/analytic tools; Z.E. and H.S. performed and analyzed PBMC-based neutralization assays; Y.L. performed carbohydrate microarray analyses; P.N.P.G. performed and analyzed neutralization assays using viral strains produced in GnTI −/− cells; D.I.R.S. isolated and characterized the NA2 glycan; M.S.S. performed and analyzed TZM-bl neutralization assays; ...
In this study, expanded human trial with M, Gerbil kidney tissue culture inactivated HFRS vaccine was carried out and neutralizing antibody response was assessed by plaque reduction neutralization(PRNT) and CPE neutralization(CPENT) methods. According to the data of all 74 person immune sera assayed by the two methods, the rates of seroconversion and GMT tesed by CPENT were significantly higher than that by PRNT. Several vaccinating groups were studied and the neutralizing antibody levels were as follows: v...
There has also been a steady boost in expertise in other sorts of antiviral antibodies as well as their effector features That could be crucial for vaccines. This Assembly aims to go over a range of topics such as: 1) First virus transmission events for vaccine intervention, two) Non-neutralizing antibody correlates of sterilizing immunity; three) Epitopes, constructions and ontogeny of broadly neutralizing antibodies; four) Novel vaccine ideas for broadly neutralizing antibody induction; and 5) Immunotherapy. Emphasis will likely be placed on recent unpublished conclusions in key parts that keep the best guarantee for quick progress towards a powerful vaccine ...
Background:. - VRC01 is a manmade antibody directed against the human immunodeficiency virus (HIV). Antibodies fight infection. Researchers eventually want to know if VRC01 helps prevent or treat HIV infection. In this study they want to know if the study drug is safe if taken in a vein or under the skin. Taking VRC01 in this study will not protect against HIV infection.. Objectives:. - To see if VRC01 and placebo are safe and well tolerated.. Eligibility:. - Healthy adults 18 to 50 years old.. Design:. ...
In spite of 25 years of intensive research, no effective human immunodeficiency virus type 1 (HIV-1) vaccine has yet been developed. One reason for this is that investigators have concentrated mainly...
Some 25 years after the AIDS epidemic spawned a worldwide search for an effective vaccine against the human immunodeficiency virus, progress in the field seems to have effectively become stalled. The reason? According to new findings, its at least partly due to the fact that our bodys natural HIV antibodies simply dont have a long enough reach to effectively neutralize the viruses they are meant to target.
The identification of a single-CD4 bound asymmetric HIV-1 Envelope trimer intermediate provides new mechanistic insights into the activation of Envelope for fusion, and highlights the importance of asymmetry in biology.
Prohibitin antibody for detecting human prohibitin. Validated on up to 12 cell lysates for western blotting. Try a trial size today.
Synaptic Systems strives to provide you with the best antibodies in neuroscience and cell biology. Most antibodies are exclusively available from Synaptic Systems and have been developed in-house in close collaboration with renowned experts in the field. Our antibodies are well characterized and known for their excellent quality. We are constantly adding new products and offer attractive licensing conditions ...
These ARC antibodies can be used for Western Blot, ELISA, and other applications. Find the antibody products you need for your research online from ProSci!
Bricault CA, Kovacs JM, Nkolola JP, Yusim K, Giorgi EE, Shields JL, Perry J, Lavine CL, Cheung A, Ellingson-Strouss K, Rademeyer C, Gray GE, Williamson C, Stamatatos L, Seaman MS, Korber BT, Chen B, Barouch DH. A multivalent clade C HIV-1 Env trimer cocktail elicits a higher magnitude of neutralizing antibodies than any individual component. J Virol. 2015 Mar; 89(5):2507-19 ...
In the new study, researchers have developed a method to rapidly produce specific human antibodies in the laboratory itself from B-cells isolated from patient blood samples and by replicating the same processes these cells use in the body to prevent infections.
Mouse Monoclonal Anti-IL-12 p70/IL-12A Antibody (2Y37). Validated: WB, Flow, CyTOF-ready. Tested Reactivity: Human. 100% Guaranteed.
The botulinum neurotoxins (BoNTs) are category A biothreat agents which have been the focus of intensive efforts to develop vaccines and antibody-based prophylaxis and treatment. Such approaches must take into account the extensive BoNT sequence variability; the seven BoNT serotypes differ by up to 70% at the amino acid level. Here, we have analyzed 49 complete published sequences of BoNTs and show that all toxins also exhibit variability within serotypes ranging between 2.6 and 31.6%. To determine the impact of such sequence differences on immune recognition, we studied the binding and neutralization capacity of six BoNT serotype A (BoNT/A) monoclonal antibodies (MAbs) to BoNT/A1 and BoNT/A2, which differ by 10% at the amino acid level. While all six MAbs bound BoNT/A1 with high affinity, three of the six MAbs showed a marked reduction in binding affinity of 500- to more than 1,000-fold to BoNT/A2 toxin. Binding results predicted in vivo toxin neutralization; NlAbs or MAb combinations that ...
EMD-8573 -- Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial. -- Easterhoff D, Moody MA, Fera D, Cheng H, Ackerman M, Wiehe K, Saunders KO, Pollara J, Vandergrift N, Parks R, Kim J, Michael NL, OConnell RJ, Excler JL, Robb ML, Vasan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Sinangil F, Tartaglia J, Phogat S, Kepler TB, Alam SM, Liao HX, Ferrari G, Seaman MS, Montefiori DC, Tomaras GD, Harrison SC, Haynes BF -- The Electron Microscopy Data Bank (EMDB) is a public repository for electron microscopy density maps of macromolecular complexes and subcellular structures. It covers a variety of techniques, including single-particle analysis, electron tomography, and electron (2D) crystallography. The EMDB was founded at EBI in 2002, under the leadership of Kim Henrick. Since 2007 it has been operated jointly by the PDBe, and the Research
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The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic ...

Broadly Neutralizing Antibodies - IAVIBroadly Neutralizing Antibodies - IAVI

Vaccines against viral diseases typically work because they elicit antibodies against the virus that prevent infection. Given ... Broadly Neutralizing Antibodies Vaccines against viral diseases typically work because they elicit antibodies against the virus ... referred to as broadly neutralizing antibodies (bnAbs). These antibodies are effective against the majority of HIV isolates ... Antibodies for other diseases. Opportunities for novel approaches to developing antibody products exist across the spectrum of ...
more infohttps://www.iavi.org/our-science/broadly-neutralizing-antibodies

Cell Based Neutralizing Antibody AssaysCell Based Neutralizing Antibody Assays

... Cell-based anti-drug neutralizing antibody (NAb) assays for safety and efficacy ... Experienced cell-based neutralizing antibody assay capabilities. Our experts, based in Good Laboratory Practice (GLP) compliant ... Cell-based neutralizing antibody assays can be difficult to develop as the selection of the most suitable assay type (indirect ... Cell-based assays mimic the mechanism by which the neutralizing antibodies (NAbs) exert their effect in vivo and are the ...
more infohttp://www.intertek.com/pharmaceutical/immunochemistry/cell-based-assays/

Broadly Neutralizing Antibody Combinations | AVACBroadly Neutralizing Antibody Combinations | AVAC

Overview of the combinations of broadly neutralizing antibodies (bNAbs) under investigation in early clinical studies for HIV ... Overview of the combinations of broadly neutralizing antibodies (bNAbs) under investigation in early clinical studies for HIV ...
more infohttps://www.avac.org/infographic/bnab-combinations

Role of neutralizing antibodies in HIV infection.  - PubMed - NCBIRole of neutralizing antibodies in HIV infection. - PubMed - NCBI

Role of neutralizing antibodies in HIV infection.. Haigwood NL1, Stamatatos L. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/15080182?dopt=Abstract

Broadly neutralizing antibodies to prevent HIV-1 | ScienceBroadly neutralizing antibodies to prevent HIV-1 | Science

These are referred to as broadly neutralizing antibodies (bnAbs). Such antibodies can be detected in about 25% of persons with ... Studies show the potential of synthetic and combinations of broadly neutralizing antibodies ... Studies show the potential of synthetic and combinations of broadly neutralizing antibodies ... Advances in technology-especially single-cell antibody cloning techniques-have led to the isolation and characterization of ...
more infohttp://science.sciencemag.org/content/358/6359/46.summary

Neutralizing Antibodies
     Summary Report | CureHunterNeutralizing Antibodies Summary Report | CureHunter

Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus. ... Neutralizing Antibodies. Subscribe to New Research on Neutralizing Antibodies Antibodies that reduce or abolish some biological ... of anti-PE neutralizing antibodies in vivo and was less susceptible to inactivation by anti-PE neutralizing antibodies compared ... highly neutralizing antibody response in the clearance of Hepatitis C virus (HCV) infection. ". 10/01/2015 - "Neutralizing ...
more infohttp://www.curehunter.com/public/keywordSummaryD057134-Neutralizing-Antibodies.do

Broadly Neutralizing Antibodies in HIV Patients | The Scientist Magazine®Broadly Neutralizing Antibodies in HIV Patients | The Scientist Magazine®

... and the infection itself that influence whether a person with HIV will produce broadly neutralizing antibodies. ... broadly neutralizing antibodies. disease/medicine. HIV. HIV vaccine. infectious disease. vaccination. vaccine. ... Broadly Neutralizing Antibodies in HIV Patients. Researchers identify aspects of the patient, the virus, and the infection ... WIKIMEDIA, BRUCEBLAUSEOnly about 1 percent of HIV-infected people will generate the broadly neutralizing antibodies that target ...
more infohttps://www.the-scientist.com/the-nutshell/broadly-neutralizing-antibodies-in-hiv-patients-32797

Immunogenicity and Neutralizing Antibody | Life Sciences | SGSImmunogenicity and Neutralizing Antibody | Life Sciences | SGS

Home › Life Sciences › Clinical Research Services › Bioanalytical Services › Immunogenicity and Neutralizing Antibody ... Life Sciences Immunogenicity and Neutralizing Antibody. SGS has been working in the immunoanalysis and immunogenicity testing ... Immunogenicity screening assays (peptide/protein drugs and therapeutic monoclonal antibodies): *Detection of anti-drug antibody ...
more infohttps://www.sgs.com/en/life-sciences/clinical-research-services/bioanalytical-services/immunogenicity-and-neutralizing-antibody

Broadly Neutralizing Antibodies in HIV Patients | The Scientist Magazine®Broadly Neutralizing Antibodies in HIV Patients | The Scientist Magazine®

Broadly Neutralizing Antibodies in HIV Patients. Broadly Neutralizing Antibodies in HIV Patients. Researchers identify aspects ... broadly neutralizing antibodies. disease/medicine. HIV. HIV vaccine. infectious disease. vaccination. vaccine. ... WIKIMEDIA, BRUCEBLAUSEOnly about 1 percent of HIV-infected people will generate the broadly neutralizing antibodies that target ... Thirdly, different virus subtypes appeared more or less likely to trigger the production of broadly neutralizing antibodies. ...
more infohttps://www.the-scientist.com/the-nutshell/broadly-neutralizing-antibodies-in-hiv-patients-32797/amp

Link Between Apobec3 Gene, Neutralizing Antibody Revealed | EmaxHealthLink Between Apobec3 Gene, Neutralizing Antibody Revealed | EmaxHealth

A single gene controls the ability of mice to make neutralizing antibodies against this retrovirus and to recover from the ... "This research delineates a potential genetic mechanism behind the production of neutralizing antibodies to HIV, which are ... Given that Apobec3 seems to help the immune system make neutralizing antibodies against retroviruses, the destruction of ... Antibodies are key to warding off viral infections, and most vaccines against viral diseases stimulate the body to make ...
more infohttps://www.emaxhealth.com/2/24/24596.html

The rise of broadly neutralizing antibodies | EATGThe rise of broadly neutralizing antibodies | EATG

Research on broadly neutralizing antibodies (bNAbs) is taking the field of HIV prevention science in new directions, with ...
more infohttp://www.eatg.org/news/the-rise-of-broadly-neutralizing-antibodies/

Neutralizing antibody - WikipediaNeutralizing antibody - Wikipedia

The difference between neutralizing antibodies and binding antibodies is that neutralizing antibodies neutralize the biological ... A neutralizing antibody (NAb) is an antibody that defends a cell from an antigen or infectious body by neutralizing any effect ... are commonly targeted by neutralizing antibodies. A few examples are Rebif, Betaseron and Avonex. Blocking antibody Mike Recher ... Neutralizing antibodies have shown potential in the treatment of retroviral infections. Medical professionals and researchers ...
more infohttps://en.wikipedia.org/wiki/Neutralizing_antibody

Diagnostic Applicability of Neutralizing Antibodies to Trypanosoma cruzi Trans-sialidase.  - PubMed - NCBIDiagnostic Applicability of Neutralizing Antibodies to Trypanosoma cruzi Trans-sialidase. - PubMed - NCBI

Diagnostic Applicability of Neutralizing Antibodies to Trypanosoma cruzi Trans-sialidase.. Leguizamón MS1,2. ... The method described here, termed trans-sialidase inhibition assay (TIA), enables the detection of TS-neutralizing antibodies ... TIA; Trans-sialidase; Trans-sialidase-neutralizing antibodies; Trypanosoma cruzi human diagnosis; Trypanosoma cruzi reservoirs ... cruzi infection correlates with the elicitation of antibodies directed to the TS catalytic domain, which inhibit the sialyl ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/30868532

Broadly Neutralizing Antibodies | A&U MagazineBroadly Neutralizing Antibodies | A&U Magazine

Broadly neutralizing antibodies (bNAbs) hold the potential of being a component of an HIV functional cure regimen, an HIV ... Broadly neutralizing antibodies aim for a diverse effect against HIV types. by Jeannie Wraight and David Miller ... recently identified monoclonal antibodies that appear capable of a broadly neutralizing effect on a diverse range of HIV ... more than any other broadly neutralizing antibodies previously discovered.. The most promising bNAbs of the group will be ...
more infohttps://aumag.org/2018/09/07/broadly-neutralizing-antibodies/

JCI -
Towards HIV-1 remission: potential roles for broadly neutralizing antibodiesJCI - Towards HIV-1 remission: potential roles for broadly neutralizing antibodies

Recently discovered broadly neutralizing antibodies (bNAbs) exhibit remarkable breadth and potency in their ability to ... bNAbs can prevent infection by directly neutralizing cell-free virions, which prevents infection and accelerates viremia ... decline through antibody-mediated viral clearance. (. B. ) bNAbs can potentially bind to infected cells and mediate antiviral ...
more infohttps://www.jci.org/articles/view/80561/figure/1

Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy | SpringerLinkSystemic delivery of neutralizing antibody targeting CCL2 for glioma therapy | SpringerLink

Loberg RD, Ying C, Craig M et al (2007) Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate ... Scholl SM, Pallud C, Beuvon F et al (1994) Anti-colony-stimulating factor-1 antibody staining in primary breast adenocarcinomas ... Carton JM, Sauerwald T, Hawley-Nelson P et al (2007) Codon engineering for improved antibody expression in mammalian cells. ... specific antibodies. Hum Antibodies 16:117-125PubMedGoogle Scholar ...
more infohttps://link.springer.com/article/10.1007%2Fs11060-010-0473-5

Viruses | Free Full-Text | Recombinant Sheep Pox Virus Proteins Elicit Neutralizing AntibodiesViruses | Free Full-Text | Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies

Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, ... To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV ... The aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (SPPV; genus Capripoxvirus ... Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies. Olga V. Chervyakova 1. ...
more infohttp://www.mdpi.com/1999-4915/8/6/159

Powerful HIV-Neutralizing Antibody s Pictures Revealed By Scripps ResearchersPowerful HIV-Neutralizing Antibody s Pictures Revealed By Scripps Researchers

Researchers at The Scripps Research Institute have uncovered the surprising details of how a powerful anti-HIV antibody grabs ... in smaller concentrations of antibody molecules than any previously reported broadly neutralizing anti-HIV antibody. The new ... Powerful HIV-Neutralizing Antibody s Pictures Revealed By Scripps Researchers. by Tanya Thomas on October 16, 2011 at 3:12 PM ... Since the 1990s, Burton, Wilson, and other researchers have been searching for such "broadly neutralizing" antibodies against ...
more infohttp://www.medindia.net/news/Powerful-HIV-Neutralizing-Antibodys-Pictures-Revealed-By-Scripps-Researchers-92031-1.htm

Combining Broadly Neutralizing Antibodies Shows Promise - TheBodyPRO.comCombining Broadly Neutralizing Antibodies Shows Promise - TheBodyPRO.com

Results from the first human trials of a dual broadly neutralizing antibodies regimen appeared effective, safe, and well ... Slight Changes to Broadly Neutralizing HIV Antibody Yield Great Dividends No Proof of New HIV Cure, Despite Headlines -- Heres ... Slight Changes to Broadly Neutralizing HIV Antibody Yield Great Dividends No Proof of New HIV Cure, Despite Headlines -- Heres ... Rockefeller University presented evidence that early administration of a short course of two broadly neutralizing antibodies ( ...
more infohttp://www.thebodypro.com/content/81404/combining-broadly-neutralizing-antibodies-shows-pr.html?ic=2005

JCI -
Human IgG Fc domain engineering enhances antitoxin neutralizing antibody activityJCI - Human IgG Fc domain engineering enhances antitoxin neutralizing antibody activity

The effector activity of antibodies is dependent on engagement with Fcγ receptors (FcγRs) and activation of the associated ... engaging activating FcγRs substantially enhanced the in vitro and in vivo activity of anthrax toxin-neutralizing antibodies. ... These findings indicate that the application of Fc domain engineering is a feasible strategy to enhance toxin-neutralizing ... we used mice expressing only human FcγRs to evaluate the contribution of FcγR-mediated pathways to the neutralizing activity of ...
more infohttps://www.jci.org/articles/view/72676/figure/3

NIH-supported scientists elicit broadly neutralizing antibodies to HIV in calves | EurekAlert! Science NewsNIH-supported scientists elicit broadly neutralizing antibodies to HIV in calves | EurekAlert! Science News

... eliciting broadly neutralizing antibodies (bNAbs) to HIV by immunizing calves. The findings offer insights for HIV vaccine ... design, and support further study of modified bovine antibodies as HIV therapeutics or prevention tools in humans, scientists ... NIH-supported scientists elicit broadly neutralizing antibodies to HIV in calves Unique structure of bovine bNAbs may inform ... Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows. Nature DOI: 10.1038/nature23301 (2017). ...
more infohttps://www.eurekalert.org/pub_releases/2017-07/nioa-nse071717.php

JCI -
Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearanceJCI - Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance

Antibody response to hypervariable region 1 interferes with broadly neutralizing antibodies to hepatitis C virus. J Virol. 2016 ... This plasma might contain NAbs similar to known broadly neutralizing monoclonal antibodies (bNmAbs), broadly neutralizing ... Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proc Natl Acad Sci U S A. 2012 ... Neutralizing antibody response during acute and chronic hepatitis C virus infection. Proc Natl Acad Sci U S A. 2004;101(27): ...
more infohttps://jci.org/articles/view/130720

Frontier Biotech licenses 3BNC117, a novel broad-spectrum HIV neutralizing antibodyFrontier Biotech licenses 3BNC117, a novel broad-spectrum HIV neutralizing antibody

... Tuesday, July 25, 2017 AIDS/HIV News ... 3BNC117, a novel broad-spectrum HIV neutralizing antibody, with albuvirtide for the treatment and prophylaxis of HIV infection ... 3BNC117 is one of the most effective broad-spectrum HIV neutralizing antibodies. Several phase 1 and phase 2 clinical trials ... www.prnewswire.com/news-releases/frontier-biotech-licenses-3bnc117-a-novel-broad-spectrum-hiv-neutralizing-antibody-300493440. ...
more infohttp://www.medindia.net/health-press-release/Frontier-Biotech-licenses-3BNC117-a-novel-broad-spectrum-HIV-neutralizing-antibody-335092-1.htm

Rapid evolution of the neutralizing antibody response to HIV type 1 infection | PNASRapid evolution of the neutralizing antibody response to HIV type 1 infection | PNAS

Variable individual autologous neutralizing responses. The autologous neutralizing antibody responses are displayed for seven ... broadly neutralizing monoclonal antibodies (b12, 2F5, and 2G12) (Table 5; refs. 22-24). Monoclonal antibody neutralization ... peak neutralizing antibody titers reached ,1,000 as exemplified in patient TN-1. For two patients, negligible neutralizing ... generating low levels of neutralizing antibody or antibody restricted to the autologous strain and laboratory-adapted strains ...
more infohttps://www.pnas.org/content/100/7/4144?ijkey=f513d2b828aa3899208243263d344e622ddfd978&keytype2=tf_ipsecsha
  • Cell-based assays mimic the mechanism by which the neutralizing antibodies (NAbs) exert their effect in vivo and are the regulatory authorities' preferred method to detect NAb presence. (intertek.com)
  • Cell-based neutralizing antibody assays can be difficult to develop as the selection of the most suitable assay type (indirect or direct) and format depends on thorough understanding of the drug's mechanism of action. (intertek.com)
  • Through the intelligent and experienced application of cell-based neutralizing antibody assays, Intertek is the ideal partner for your biologic drug development or pharmacovigilance requirements for immunogenicity testing . (intertek.com)
  • Henipavirus serological analyses (Luminex multiplexed binding and inhibition assays, virus neutralisation tests and western blots) and lyssavirus serological analyses (LBV: modified Fluorescent Antibody Virus Neutralisation test, LBV and Mokola virus: lentivirus pseudovirus neutralisation assay) were undertaken on 73 and 70 samples respectively. (plos.org)
  • However, the presence of antibodies against henipaviruses was detected using the Luminex binding assay and confirmed using alternative assays. (plos.org)
  • Neutralising antibodies to LBV were detected in one bat using both assays. (plos.org)
  • Scientists have uncovered new evidence that strengthens the link between a host-cell gene called Apobec3 and the production of neutralizing antibodies to retroviruses. (emaxhealth.com)
  • This research delineates a potential genetic mechanism behind the production of neutralizing antibodies to HIV, which are critical to preventing HIV infection," says NIAID Director Anthony S. Fauci, M.D. "Further research on the function of human Apobec3 could yield promising insights that inform the discovery of HIV drugs and vaccines. (emaxhealth.com)
  • While a vaccine "trains" the immune system to generate antibodies and other immune responses, passive immunization requires that the antibodies be delivered directly into the body through infusions or injections. (iavi.org)
  • Antibody preventives, if effective, could augment existing HIV prevention strategies and help limit the spread of the virus until a vaccine is developed. (iavi.org)
  • A vaccine that can elicit a broadly neutralizing effect is needed for a vaccine to be fully effecive for everyone. (aumag.org)
  • What's unexpected and unique about this antibody is that it not only attaches to the sugar coating of the virus but also reaches through to grab part of the virus's envelope protein," said the report's co-senior author Dennis Burton, a professor at The Scripps Research Institute and scientific director of the International AIDS Vaccine Initiative's (IAVI) Neutralizing Antibody Center, based on the Scripps Research La Jolla campus. (medindia.net)
  • The findings offer insights for HIV vaccine design, and support further study of modified bovine antibodies as HIV therapeutics or prevention tools in humans, scientists reported in a paper published online today in Nature . (eurekalert.org)
  • Instead, Zhu explained, they have to "reverse engineer" the right vaccine candidates using rare effective antibodies from HIV-positive patients as guides. (scripps.edu)
  • Each sample showed the antibody in a different stage of development, giving researchers a possible guide for how to elicit these antibodies with a vaccine. (scripps.edu)
  • He repeatedly donated blood over the course of a year, which researches used to create a timeline of changes in his virus' gp120, his antibody response and the ultimate emergence of a bNAb. (wikipedia.org)
  • A screen of massive gp120 libraries led to one that strongly bound both an original antibody and the mature bNAb that evolved from it. (wikipedia.org)
  • Giving patients a modified gp120 that contains little more than the epitope that both antibodies target could act to "prime" the immune system, followed by a booster that contains trimer spikes in the most natural configuration possible. (wikipedia.org)
  • The scientists also spotted a hurdle they will have to overcome as they engineer their own antibodies: The teenage VRC01 has a slightly longer amino acid chain at one site than the mature version, and this chain clashes with part of the glycoprotein shield (gp120) on HIV and prevents the antibody from effectively neutralizing the virus. (scripps.edu)
  • We knew that Apobec3 had very interesting antiviral properties, but this new discovery that it affects antibody responses will generate even greater interest in both Apobec3 and Vif. (emaxhealth.com)
  • The method described here, termed trans-sialidase inhibition assay (TIA), enables the detection of TS-neutralizing antibodies in serum samples of different mammalian species, without the use of conjugated secondary reagents. (nih.gov)
  • Other research is also starting to suggest that you can grab onto two glycans and a beta strand and get very potent and broad neutralizing antibodies against HIV," Wilson said. (medindia.net)
  • While cattle do not naturally acquire the human virus HIV, their immune systems have unique features that the researchers thought would allow them to produce potent antibodies when injected with HIV immunogens, or proteins designed to mimic proteins on the surface of HIV. (eurekalert.org)
  • It also can do so much more potently in other words, in smaller concentrations of antibody molecules than any previously reported broadly neutralizing anti-HIV antibody. (medindia.net)
  • LA, JOLLA, CA - April 5, 2016 - Scientists at The Scripps Research Institute (TSRI) and collaborating institutions have described the first-ever immature or "teenage" antibody found in a powerful class of immune molecules effective against HIV. (scripps.edu)
  • A recombinant virus assay was used to characterize in detail neutralizing antibody responses directed at circulating autologous HIV in plasma. (pnas.org)
  • A recombinant virus assay initially developed to measure antiretroviral drug resistance during a single round of virus replication was adapted to measure virus-antibody neutralization ( 19 ). (pnas.org)
  • Researchers at The Scripps Research Institute have uncovered the surprising details of how a powerful anti-HIV antibody grabs hold of the virus. (medindia.net)
  • Researchers from the current team recently isolated the new antibody and 16 others from the blood of HIV-infected volunteers, in work they reported online in the journal Nature on August 17, 2011. (medindia.net)
  • The researchers studied samples taken from the patient over five years, starting in 2006 when Zhu said the antibody was a "toddler. (scripps.edu)
  • The researchers managed to tweak the immature antibody to make it into a broadly neutralizing antibody. (scripps.edu)
  • The researchers also noted that this is the first time a VRC01-like antibody has been isolated from a patient of Asian descent-the other VRC01s had come from African or Caucasian patients. (scripps.edu)
  • IAVI and partners are expanding their antibody discovery, optimization, and manufacturing expertise to develop antibody products for prevention and therapy of multiple diseases. (iavi.org)
  • At the same time that discovery and development of these potential products are occurring, IAVI is working to ensure that future antibody treatments and preventives will be affordable and accessible to the people who need them. (iavi.org)
  • Discovered and developed by Dr. Michel Nussenzweig , head of the Laboratory of Molecular Immunology, Zanvil A. Cohn and Ralph M. Steinman Professor of The Rockefeller University , as well as a Howard Hughes Medical Institute investigator, 3BNC117 is one of the most effective broad-spectrum HIV neutralizing antibodies. (medindia.net)
  • These antibodies are effective against the majority of HIV isolates currently in circulation around the globe. (iavi.org)
  • Technological advances have made it possible to identify, characterize, optimize, and manufacture antibodies like never before. (iavi.org)
  • The majority of antibodies directed against the viral envelope glycoprotein (Env) recognizes nonneutralizing epitopes of glycoprotein monomers and is ineffectual ( 2 , 3 ). (pnas.org)
  • Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations. (pnas.org)
  • The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. (mdpi.com)
  • The principal neutralizing determinant (PND) of human immunodeficiency virus (HIV)-1 resides within the V3 loop of the envelope protein. (sciencemag.org)
  • Scholl SM, Pallud C, Beuvon F et al (1994) Anti-colony-stimulating factor-1 antibody staining in primary breast adenocarcinomas correlates with marked inflammatory cell infiltrates and prognosis. (springer.com)
  • We determined that Fc domain variants that were capable of selectively engaging activating FcγRs substantially enhanced the in vitro and in vivo activity of anthrax toxin-neutralizing antibodies. (jci.org)
  • Zhu and his colleagues were surprised to find that the antibody evolved rapidly between 2006 and 2008, gaining many of the traits it would need to fight HIV. (scripps.edu)
  • The scientists who conducted the study hypothesize that Apobec3 in humans might play a similar role in helping shape the neutralizing antibody response to human retroviruses such as HIV. (emaxhealth.com)
  • These findings add a new and quite unexpected dimension to our understanding of Apobec3 biology that might help us attack the HIV neutralizing antibody problem, an area where scientific progress has been slow," says Warner C. Greene M.D., Ph.D., director of the Gladstone Institute of Virology and Immunology and the study's principal investigator. (emaxhealth.com)
  • To determine the assay-specific cutoff value, quences and virus were detected in respiratory swab sam- we tested 124 confirmed MERS-CoV antibody-negative and ples, predominantly from juvenile dromedaries ( 5 , 10 ). (cdc.gov)
  • The new finding about Apobec3 suggests that this gene may influence anti-HIV antibody production and may help explain why some people who are repeatedly exposed to the virus never become infected. (emaxhealth.com)
  • Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. (mdpi.com)
  • To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. (mdpi.com)
  • In this report, we used mice expressing only human FcγRs to evaluate the contribution of FcγR-mediated pathways to the neutralizing activity of an anti-anthrax toxin chimeric mAb. (jci.org)
  • Similarly, survival was modestly prolonged in severe combined immunodeficiency mice bearing intracranial human U87 glioma xenografts treated with both anti-human CCL2 mAb and anti-mouse CCL2 antibodies (2 mg/kg/dose for each, twice a week) compared to mice treated with control IgG ( P = 0.0159). (springer.com)
  • Unlike human antibodies, cattle antibodies are more likely to bear unique features and gain an edge over complicated HIV immunogens. (eurekalert.org)
  • This is actually the first example of how we can go back to the really early stage to see how this antibody lineage was born and can develop," said TSRI biologist Jiang Zhu, who served as co-senior author of the study. (scripps.edu)
  • Now we know these specialized antibodies can evolve in just one or two years," added TSRI Research Associate Yajing Chen, who served as co-first author of the study with Leopold Kong (formerly of TSRI, now at NIH), TSRI Staff Scientist Linling He, and Bin Ju, Jiandong Liu and Li Ren of the China CDC. (scripps.edu)