• We use the HIV envelope protein (gp120/gp41) as a model system. (stanford.edu)
  • 4E10 is the broadest HIV-1 nAb known to date and recognizes a contiguous and highly conserved helical epitope in the membrane-proximal region of gp41. (rcsb.org)
  • Over 250 crystal structures of monoclonal Fab fragments and complexes with a variety of antigens, such as peptides, steroids, cocaine, and proteins, including HIV-1, gp120 and gp41, have led to significant insights into antibody-antigen recognition, virus neutralization, and vaccine design for HIV-1. (scripps.edu)
  • We have also determined structures of almost all of the rare, broadly neutralizing antibodies against the HIV-1 envelope proteins, gp120 and gp41, in order to elucidate the sites of vulnerability that can be used for HIV-1 vaccine design. (scripps.edu)
  • HIV-1 envelope gp41 broadly neutralizing antibodies: hurdles for vaccine development. (duke.edu)
  • The HIV-1 envelope (Env) glycoproteins are produced as a 160 kDa polyprotein that is subsequently processed to yield virion-associated, trimeric complexes of non-covalently associated gp120-gp41 heterodimers [ 1 , 2 ]. (plos.org)
  • However, studies have suggested a more complex role of the gp41 endodomain [ 11 , 12 ], showing neutralization of HIV-1 by Abs directed to an epitope in CT of gp41 [ 13 - 15 ]. (plos.org)
  • show that immune tolerance to self-antigens impedes the generation of some broadly protective antibodies that bind to HIV gp41. (rupress.org)
  • The cover image depicts a HIV virus (orange) with viral spikes containing gp41 subunits (blue) and Y-shaped antibodies (green). (rupress.org)
  • We have demonstrated that recombinant Qβ framed with gp41 MPER of HIV can be used either alone or in combination with other strategies for the production and monitoring of HIV-1 gp41 MPER-specific immune responses. (alliedacademies.org)
  • Human immunodeficiency virus (HIV-1) entry into cells involves triggering of the viral envelope glycoprotein (Env) trimer ([gp120/gp41]3) by the primary receptor, CD4, and coreceptors, CCR5 or CXCR4. (bvsalud.org)
  • ABSTRACT The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. (unl.pt)
  • Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. (unl.pt)
  • The envelope glycoproteins (Env), gp120 and gp41, of human immunodeficiency virus type 1 (HIV-1) play a central role in viral transmission and mediate attachment and incorporation of the virus into target cells through specific interactions with the CD4 receptor and chemokine co-receptors [ 1 ]. (biomedcentral.com)
  • Keywords: HIV-1, gp120, gp41, bNAbs, Broadly neutralizing antibodies Intro A distinctive hallmark of modern-day medicine in the last decade has been the increasing use of monoclonal antibodies offering targeted therapeutic effects for a range of disorders. (ecolowood.com)
  • Of all viral proteins, only gp120 and gp41 have epitopes for antibody acknowledgement. (ecolowood.com)
  • Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. (duke.edu)
  • Standardized assays to assess vaccine and antiviral drug efficacy are critical for the development of protective HIV-1 vaccines and drugs. (plos.org)
  • Human serum usually contains natural IgG, IgM and IgA antibodies, generated independently of any exposure to foreign antigens or vaccines or elicited in the course of infectious or autoimmune diseases. (biomedcentral.com)
  • As of now, more than 100 DNA- and RNA-based vaccines have advanced to clinical development for SARS-CoV-2, HIV, other infectious diseases, and cancers. (nih.gov)
  • The Structural Biology Section (SBS) seeks to apply structural biology to the development of effective vaccines - especially a vaccine against HIV-1. (nih.gov)
  • HIV diversity and capability for antigenic drift are only two of the reasons for the inefficiency of first-generation anti-HIV vaccines, which induced a humoral (antibody) response against a limited number of epitopes. (aphios.com)
  • Those vaccines included whole inactivated virus preparations, utilizing heat or formalin, or a recombinant envelope protein of HIV gp120. (aphios.com)
  • The envelope (Env) glycoproteins on HIV-1 virions are the sole target of broadly neutralizing antibodies (bNAbs) and the focus of vaccines. (bvsalud.org)
  • As a consequence of bNAb precursors fail to bind most recombinant HIV-1 Envs (such as those that would be used in HIV-1 vaccines). (washington.edu)
  • Thus, one potential reason for the failure of HIV-1 vaccines to elicit bNAbs is that the Env immunogens tested failed to engage bNAb precursor B cells, and thus failed to start the process of bnAb production. (washington.edu)
  • VIR-1111 HIV vaccine canidate is based on human cytomegalovirus that has been designed to elicit abundant T cells that recognize HIV epitopes in a way that differs from prior HIV vaccines. (precisionvaccinations.com)
  • The inclination of HIV-1 to rapidly accumulate mutations to escape sponsor immune reactions represents a major hurdle to the development of effective vaccines. (ecolowood.com)
  • By studying SARS-CoV-2 spike protein mutations, its ability to diversify and adapt, as well as antibody interactions we aim to create a pipeline to enable better understanding of these and future pathogens and ways to fight them in early stages through vaccines and new drug development. (lu.se)
  • Disentangling and visualizing the key epitopes for neutralizing antibodies against SARS-CoV-2 at the atomic level - Implications for development of vaccines against COVID-19. (lu.se)
  • These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load. (nature.com)
  • This discovery will likely have a tremendous impact on the research conducted in the field of HIV cure both at basic and therapeutic approaches. (europa.eu)
  • to gather information from the natural evolution of B cell responses to inform effective immunogen designs, and to identify prophylactic and therapeutic antibody-based countermeasures. (nih.gov)
  • SNAP might also provide a means to persistently deliver prophylactic or therapeutic levels of antibodies or antibody derivatives, thereby supplying affordable, timely and sustainable global access to these HIV interventions. (nih.gov)
  • Our therapeutic HIV/AIDS vaccine consists of an inactivated a strain of HIV, inactivated by three orthogonal methods: a genetic method to attenuate the virus, a physical method called CFI and a chemical method called AT-2. (aphios.com)
  • We are seeking global partnerships for developing an HIV therapeutic vaccine that could lead to a functional cure for HIV/AIDS patients. (aphios.com)
  • In addition, the findings can guide the formulation of effective antibody combinations for therapeutic use. (bvsalud.org)
  • Potent, broadly HIV-1 neutralizing antibodies (nAbs) may be invaluable for the design of an AIDS vaccine. (rcsb.org)
  • Neutralizing antibodies (NAbs) can block virus entry by binding Env and inhibiting attachment or conformational changes required for fusion [ 4 - 7 ]. (plos.org)
  • The initial anti-Env antibody response is nonneutralizing (28), but within 1 or 2 2 months after infection, neutralizing antibodies (NAbs) emerge which tend to be highly strain specific for the autologous virus and exhibit little or no neutralizing activity against heterologous HIV-1 strains (10, 22). (woofahs.com)
  • Detailed analyses of the epitope specificities of broad plasma neutralizing antibody responses performed by several groups revealed the presence in HIV-positive (HIV+) plasmas of NAbs with as yet undefined epitope specificities (1, 15, 18, 23). (woofahs.com)
  • Similar to the infection of humans by HIV-1, chronic infection of rhesus macaques by simian/human immunodeficiency viruses (SHIVs) or chimpanzees by HIV-1 also results in the elicitation of potent NAbs against the autologous virus and, to a much lesser extent, against heterologous SHIV isolates or HIV-1 viruses (3, 6, (R)-(-)-Mandelic acid 12, 17). (woofahs.com)
  • HIV-specific neutralizing antibodies (nAbs) bind to the HIV envelope (Env), a protein on the surface of the viral particle that binds CD4 receptors on T-cells and mediates entry into the cell. (fredhutch.org)
  • Such nAbs are likely to protect against mother-to-child transmission (MTCT) of HIV. (fredhutch.org)
  • The authors hypothesized that selection for transmission of a particular maternal HIV variant, and not others, could be partially mediated by maternal nAbs. (fredhutch.org)
  • They found that the plasma more potently neutralized the HIV variants compared to the individual nAbs, suggesting that neutralization activity might be mediated by antibodies that were not isolated in the screen. (fredhutch.org)
  • Nonetheless, removal of particular glycans that normally coat the Env protein to block recognition by the immune system made the viruses more sensitive to neutralization, suggesting the exposure of a critical epitope in Env targeted by nAbs. (fredhutch.org)
  • They found that several nAbs mediated ADCC against a "Tier 2" HIV variant. (fredhutch.org)
  • Then, using ELISA and a phage immunoprecipitation method (PhIP), they identified the V3 region in Env as the epitope for these antibodies, suggesting that V3-specific nAbs might have a role in ADCC in MTCT. (fredhutch.org)
  • Description: The RPA-T4 monoclonal antibody reacts with human CD4, a 59 kDa cell surface receptor expressed by a majority of thymocytes, subpopulation of mature T cells (T-helper cells) and in low levels on monocytes. (thermofisher.com)
  • Description: The MBSA43 monoclonal antibody reacts with human T cell immunoreceptor with Ig and ITIM domains (TIGIT), which is also known as VSTM3 or WUCAM. (thermofisher.com)
  • These mAbs were found to bind epitopes harbored in the M77 Fab fragment. (tau.ac.il)
  • Several HIV-1 ALVAC/AIDSVAX vaccinee-derived monoclonal antibodies (MAbs) specific for the gp120 first constant (C1) region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. (duke.edu)
  • Among the C1-specific MAbs that showed Galcer blocking, the antibody-dependent cellular cytotoxicity-mediating CH38 IgG and its natural IgA isotype were the most potent blocking antibodies. (duke.edu)
  • With the recent acquisition of the technology created by BioClonetics Immunotherapeutics, Inc., the Company has additional and complementary technology for producing fully human monoclonal antibodies (mAbs) that neutralize the HIV virus. (advfn.com)
  • The targeted epitope has remained present in 98% (either directly or by way of conserved substitutions) of all now known 87,336 HIV isolates analyzed by the Company's use of artificial intelligence.The failure of other mAbs, such as the Vaccine Research Group VRC01 [Bar KJ, et al. (advfn.com)
  • The Company has proprietary technology for producing fully human monoclonal antibodies (mAbs) against infectious diseases which is currently being employed to produce monoclonal antibody therapeutics for treating the CoronaVirus (SARS-CoV-2), HIV-1 and the Feline Leukemia virus. (nbc4i.com)
  • More recently, two additional human MAbs, PG9 and (R)-(-)-Mandelic acid PG16, were isolated from a subject infected with clade A HIV-1 and were shown to bind to a QNE that also includes the V2 and V3 loops (30). (woofahs.com)
  • Here, we describe a panel of MAbs from SHIVSF162P4-infected rhesus macaques that demonstrates extremely potent neutralization against the homologous virus (that expresses the same Env as HIV-1 SF162) and that recognizes QNEs present on the surface of intact virions. (woofahs.com)
  • Similar to the human MAbs 2909, PG9, and PG16, these rhesus macaque monoclonal antibodies (RhMAbs) recognize QNEs that include the V2 and V3 loops. (woofahs.com)
  • Our initial screen of MassBiologics' existing panel of SARS-CoVspecific antibodies resulted in Mabs with ELISA binding activity to the receptor binding domain of the SARS-CoV-2 Spike protein. (umassmed.edu)
  • We have succeeded in improving the breadth and potency of HIV-1-neutralzing antibodies, so that the best, such as VRC01.23 (Kwon 2021 Mabs 13:1946918) can neutralize ~95% of our 208-strain cross-clade panel with an IC80 of less than 1 µg/ml. (nih.gov)
  • The PG9 and 2219 epitopes became accessible for binding after conformational unmasking was induced by the pre-binding of select mAbs. (bvsalud.org)
  • HIV-1 Env gp140 proteins bound to Galcer liposomes with Kds (dissociation constants) in the nanomolar range. (duke.edu)
  • Here, we have mimicked this interaction by using an artificial membrane containing synthetic Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block the HIV-1 Env-Galcer interaction. (duke.edu)
  • Enzolytics, Inc. is a drug development company committed to commercializing its proprietary proteins and monoclonal antibodies to treat debilitating infectious diseases. (nbc4i.com)
  • The expertise at MassBiologics, particularly in the areas of Discovery and Process Development, has allowed rapid production of SARS CoV-2 proteins (including several spike proteins and N protein) and human antibodies and nanobodies , contributing to the evaluation and development of therapeutics and diagnostics. (umassmed.edu)
  • An inactivated attenuated HIV vaccine preparation, which retains the conformation of envelope proteins, may become a valuable component of such a vaccination regimen. (aphios.com)
  • Using a laboratory technique created at Johns Hopkins Medicine in 2010, the study researchers replicated the cellular environment in which specialized immune cells called antigen presenting cells (APCs) break down proteins derived from HIV and make them visible ("presented") to the immune system's frontline of defense, cells known as CD4+ T lymphocytes, or helper T cells. (technologynetworks.com)
  • When APCs chew up proteins from an antigen and present the fragments, known as antigenic epitopes, on their surface, the epitopes become visible to helper T cells and initiate an immune response. (technologynetworks.com)
  • PGT121 is a monoclonal antibody isolated in 2011 from an African donor infected with HIV-1 subtype A, whose sera had demonstrated superior neutralization breadth and potency in an observational cohort, and so was considered an 'elite neutralizer' 9 . (nature.com)
  • Our major goal is to understand the interaction and neutralization of foreign antigens by the immune system through high-resolution x-ray structural studies of antibodies, Variable Lymphocyte Rectors (VLRs) and antigens in the humoral system, T-cell receptor complexes with MHC class I and class II in the cellular system, and through pattern recognition receptors, such as TLRs, in the innate immune system. (scripps.edu)
  • 18 constructs expressing various subtypes C and CRF01_AE Envs, mostly acute, in subtype-matched and -unmatched HIV backbones were tested for functionality and neutralization sensitivity. (plos.org)
  • Our results suggest a possible effect of non- env HIV-1 genes on the interaction of Env and neutralizing antibodies and highlight the need to generate a library of IMCs representative of the HIV-1 subtype spectrum to be used as standardized neutralization assay reagents for assessing HIV-1 vaccine efficacy. (plos.org)
  • These results highlight similarities in the B-cell responses of humans and macaques to structurally complex neutralization epitopes on related viruses, HIV-1 and SHIV. (woofahs.com)
  • An effective HIV vaccine would have to stimulate the immune system to produce antibodies that can bind to the virus and prevent infection of target cells -an event known as neutralization. (fredhutch.org)
  • The investigators then tested the neutralization capacity of both the maternal plasma, which contains a mixture of all antibodies, and individual representatives of the 21 nAb families against several "Tier 1" and "Tier 2" HIV-1 viruses. (fredhutch.org)
  • The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. (elsevierpure.com)
  • Determination of the structure of the HIV-1 gp120 envelope glycoprotein (Kwong 1998 Nature 393, 648-659), provided a physical map of the primary target of neutralizing antibodies against HIV-1 and showed how gp120 conformational diversity can prevent antibody-mediated neutralization (Kwong 2002 Nature 420, 678-682) and how N-linked carbohydrates can form an "evolving glycan shield" (Wei 2003 Nature 422, 307-312). (nih.gov)
  • These epitopes become accessible after allosteric conformational changes are induced by the pre-binding of select Abs, prompting us to test if similar conformational changes are required for these Abs to exhibit their neutralization capability. (bvsalud.org)
  • We tested HIV-1 neutralization where the virus-mAb mix was pre-incubated/not pre-incubated for 1 hour prior to adding the target cells. (bvsalud.org)
  • Attempts to understand the masking mechanism led to the revelation that interaction between virus and host cells is needed to sensitize the virions for neutralization by broadly neutralizing antibodies (bNAbs). (bvsalud.org)
  • These data provide insight on how bNAbs may gain access to these occluded epitopes to exert their neutralization effects and block HIV-1 infection. (bvsalud.org)
  • Yet immunization of humans with recombinant Env leads to the production of antibodies with very narrow breadth of neutralization which fail to block infection of diverse circulating viral isolates. (washington.edu)
  • however, many CRF01_AE viruses are resistant to neutralization mediated by these antibodies. (biomedcentral.com)
  • Our data may provide important information to understand the molecular mechanism regulating the neutralization susceptibility of CRF01_AE viruses to CD4bs antibodies. (biomedcentral.com)
  • Prior to 1990, it was regarded as that antibody-mediated neutralization of HIV-1 in the sponsor was reduced and even abolished. (ecolowood.com)
  • No. 551462) can be used as the capture antibody, with recombinant soluble IL-6Ra as the standard, the Biotin Mouse Anti-Human CD126 (Cat. (bdbiosciences.com)
  • The Company is in the final development of the recombinant of the parent antibody (identified as "Clone 3"), which has been shown in in vitro tests conduction in 5 international laboratories to fully neutralized over 95% of all strains and viral subtypes of HIV-1 against which it was tested. (advfn.com)
  • CRF01_AE is a major circulating recombinant form of HIV-1 prevalent in Southeast Asia. (biomedcentral.com)
  • HIV-1 has now been classified into 9 unique subtypes and their recombinant forms [3]. (ecolowood.com)
  • Several bNAbs have been tested to date in HIV-1-infected individuals, including the CD4-binding, site-specific antibodies VRC01, 3BNC117, VRC07-523LS and N6-LS, the V3-glycan-specific antibody 10-1074 and the V2-apex-specific antibodies PGDM1400 and CAP256-VRC26.25 (refs. (nature.com)
  • Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. (advfn.com)
  • The VRC01 antibody, which we helped to identify in 2010 (Wu 2010 Science 329, 856-861), uses mimicry of the CD4 receptor to neutralize over 90 percent of HIV-1 isolates, though the inability of germline versions of VRC01 to bind to HIV-1 Env and its extraordinary level of somatic hypermutation suggest roadblocks to eliciting similar antibodies (Zhou 2010 Science 329, 811-817). (nih.gov)
  • Importantly, the Antibody Mediated Prevention (AMP) study (HVTN 704/HPTN 085) showed an IC80 of less than 1 µg/ml was required for protection by antibody VRC01. (nih.gov)
  • Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. (ebiotrade.com)
  • Epitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques. (harvard.edu)
  • IMPORTANCE: Galactosyl ceramide, a glycosphingolipid, has been postulated to be a receptor for the HIV-1 envelope glycoprotein (Env) interaction with mucosal epithelial cells. (duke.edu)
  • Animals immunized with aCL or with the cofactor beta-2 glycoprotein I (b2GPI) develop clinical manifestations of APS, including fetal loss, thrombocytopenia, and neurologic and behavioral dysfunction, along with elevated levels of aPL antibodies. (medscape.com)
  • The aCL antibodies bind to b2GPI, or a complex formed by this b2GPI is a platelet adhesin glycoprotein and cardiolipin. (medscape.com)
  • Characterization of Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Variants Selected for Resistance to a CD4-Mimetic Compound. (harvard.edu)
  • Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope glycoprotein gp120, is a high priority in HIV vaccine design. (boku.ac.at)
  • HIV-1 infection typically elicits high levels of antibodies directed against the viral surface envelope (Env) glycoprotein, gp160. (woofahs.com)
  • IMPORTANCE The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein mediates viral entry and is the sole target of neutralizing antibodies. (bvsalud.org)
  • The CD4 binding site (CD4bs) of envelope glycoprotein (Env) gp120 is a functionally conserved, important target of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. (biomedcentral.com)
  • Here we describe two IMCs derived from subtypes C and CRF01_AE HIV-1 primary isolates expressing LucR (IMC.LucR) that were engineered to express heterologous gp160 Envs. (plos.org)
  • Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. (boku.ac.at)
  • A second area in which we and others have made an impact is in understanding how human antibodies can neutralize diverse HIV-1 isolates. (nih.gov)
  • Antigen association to its corresponding binding site in the immunoglobulin molecule can elicit conformational rearrangements, generating novel epitopes termed metatopes. (tau.ac.il)
  • Binding to the epitopes was shown to require the complexation of Fab with its antigen. (tau.ac.il)
  • Denisova, G, Zwickel, J & Gershoni, JM 1995, ' Binding of HIV-1 gp120 to an anti-V3 loop antibody reveals novel antigen-induced epitopes ', FASEB Journal , vol. 9, no. 1, pp. 127-132. (tau.ac.il)
  • The association between aPL antibodies and particular human leukocyte antigen (HLA) alleles and HLA-linked epitopes has been reported in studies of patients with lupus erythematous (eg, HLA-DR7, HLA-DR4). (medscape.com)
  • and T-cell epitopes, and the heavily glycosylated portion of Reports of P. jirovecii colonization detected by molecular the antigen plays a central role in the interaction of the probes in persons ranging from healthy young children to organism with the host ( 6 - 10 , 20 ). (cdc.gov)
  • We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. (duke.edu)
  • This Antibody was verified by Cell treatment to ensure that the antibody binds to the antigen stated. (thermofisher.com)
  • The CD4 antigen is involved in the recognition of MHC class II molecules and is a co-receptor for HIV. (thermofisher.com)
  • In other words, if the antigen-antibody reaction is compared to a "key-and-lock" model, natural antibodies found in human secretions act as "passe-partout" keys to offer a background protection against most pathogens, food antigens and microbes, before the antigen-specific response can develop [ 4 ]. (biomedcentral.com)
  • One self-antigen, kynureninase, is mutated in opossums, allowing these marsupials to generate high serum antibody titers to the corresponding HIV epitope. (rupress.org)
  • Immunological tolerance to self-antigen impairs humoral responses to HIV-1. (rupress.org)
  • To further develop Dr. Cavacini's background in mucosal immunology, included in this work is structural modeling of antibody/antigen interactions to improve the design of immunotherapeutic antibodies and development of a platform for production of dimeric and secretory IgA. (umassmed.edu)
  • Our simple method, called reductionist cell-free antigen processing, reproduces in a test tube the complex events that occur in the human immune system as a response to antigens, foreign invaders to the body such as viruses like HIV," says senior study author Scheherazade Sadegh-Nasseri, Ph.D. , professor of pathology at the Johns Hopkins University School of Medicine. (technologynetworks.com)
  • One of the first critical steps in an effective antibody response is the recognition of a foreign antigen by a membrane anchored B cell receptor (BCR) on the surface of a naïve B cell. (washington.edu)
  • Expanded pools of diverse B cell clones compete for antigen and T cell help in a Darwinian process that ultimately selects for B cells with higher affinity receptors which can be secreted as soluble molecules (antibodies). (washington.edu)
  • Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. (nature.com)
  • HIV infection is efficiently controlled but not cured by Anti-Retroviral Therapy (ART) (Deeks et al. (europa.eu)
  • Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection. (harvard.edu)
  • To examine the proportion of undiagnosed HIV infection in a community sample of homosexual men. (bmj.com)
  • HIV antibody positivity was associated with increasing numbers of UAI partners, and having a sexually transmitted infection (STI) in the past year (OR 2.15). (bmj.com)
  • Therefore, it is important to assess the accuracy of self reported HIV status and the level of undiagnosed infection to determine the effectiveness of these strategies. (bmj.com)
  • GRFT can inhibit human immunodeficiency virus (HIV) infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. (mdpi.com)
  • H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. (duke.edu)
  • Natural anti-CCR5 antibodies can be decisive in preventing HIV infection in mucosal tissues and offer prompt and effective protection just at major sites of virus entry. (biomedcentral.com)
  • Therefore, characteristics of maternal HIV-specific antibodies that protect infants against infection could inform HIV vaccine design. (fredhutch.org)
  • Besides protecting against infection by neutralizing HIV, antibodies can "flag" infected cells for elimination by immune cells in a process known as antibody-dependent cell cytotoxicity (ADCC). (fredhutch.org)
  • Plasmodium falciparum infection leads to the development of protective classical and atypical memory B cell antibody responses. (rupress.org)
  • There is currently no vaccine against HIV: and AIDS, if untreated, will lead to the death of more than 95% of infected individuals 10 years post-infection. (aphios.com)
  • 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. (ebiotrade.com)
  • The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection. (ebiotrade.com)
  • Because they protect from experimental infection, it is thought that bNAbs will be an important part of an HIV-1 vaccine. (washington.edu)
  • The isolation of monoclonal bNAbs from HIV-1+ individuals has provided valuable information on how bNAbs develop during infection, and on the epitope specificities on the HIV-1 Envelope protein (Env) that an effective vaccine should aim to elicit. (washington.edu)
  • I am particularly interested in the virus-host interactions that take place when HIV establishes infection, and how HIV-2 can be used as a model to identify an HIV-1 vaccine or functional cure. (lu.se)
  • Ph.D. student, I hope to contribute to the knowledge in the field of HIV-1 plasma proteomics during acute infection and also characterize key drivers of HIV transmission and spread in Subsaharan Africa. (lu.se)
  • Increasing risk factors for leishmaniasis include urbanization, extended agricul- tural projects and civil unrest and the increase in patients with Leishmania infantum and HIV co-infection in the Region may signal a new threat. (who.int)
  • We have defined a broadly neutralizing epitope in all group 1 influenza subtypes and are working on other antibodies that recognize group 2 as well as those that cross all subtypes. (scripps.edu)
  • Though this is the first time this phenomenon has been shown with dengue, just last year there were a number of studies showing that antibodies recognize similar complex epitopes in both HIV and West Nile Virus," said de Alwis. (newstrackindia.com)
  • Immunological memory, or the ability of the adaptive immune response to recognize previously encountered pathogen epitopes with exquisite specificity and speed, is a fundamental principle in vaccine development, yet this process takes days to weeks to develop. (nih.gov)
  • Our detailed epitope Rabbit polyclonal to HNRNPM mapping analysis reveals that although the human MAb 2909 and the RhMAbs recognize that same overall Env complex region, their. (woofahs.com)
  • In the 90s, it was found that sera of HIV-1-infected individuals contained antibodies that could recognize and neutralize different subtypes of HIV-1. (ecolowood.com)
  • Included are CD4 ANTIGENS, found on T4 lymphocytes, and monocytes/macrophages, which bind to the HIV ENVELOPE PROTEIN GP120. (harvard.edu)
  • B-1 cells are found in peritoneal and pleural cavities where they provide first-line defence through antibodies able to bind polysaccharide antigens and repeated motifs that are typically found in microbial cell walls and macromolecules [ 2 , 3 ]. (biomedcentral.com)
  • As an alternative to using HIV-1 Env as a vaccine immunogen, we are pursuing a novel vaccine strategy where we generate anti-idiotypic antibodies: antibodies raised in a non-human animal model that bind with high affinity and specificity to bNAb precursors. (washington.edu)
  • 2005): Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12. (boku.ac.at)
  • In some cases, these broad neutralizing antibody responses can be mapped to the CD4-binding site of Env while in most cases a single epitope specificity cannot be identified to recapitulate the neutralizing breadth of the corresponding plasma (1, 4, 14, 15, 23, 25). (woofahs.com)
  • Consequently, we compared the fine epitope specificities of these RhMAbs to the epitope specificity of the human MAb 2909. (woofahs.com)
  • Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. (duke.edu)
  • Even though mechanisms by which the humoral response is definitely induced and managed remain elusive, new insight into broadly neutralizing HIV-1 antibodies (bNAbs) offers expanded our understanding of the antibody response. (ecolowood.com)
  • 36 million people infected and almost 2 million new infections in 2016, the need for a prophylactic HIV-1 vaccine is as urgent as ever. (washington.edu)
  • Exposure of endothelial cells to anti-b2GPI antibodies and their corresponding peptides leads to the inhibition of endothelial cell activation, as shown by decreased expression of the adhesion molecules E-selectin, intercellular adhesion molecule, and vascular cell adhesion molecule and of monocyte adhesion. (medscape.com)
  • de Alwis looked at a particular subset of the immune response - specialized molecules called antibodies. (newstrackindia.com)
  • It is possible that these undefined specificities include quaternary neutralizing epitopes (QNEs) and/or sugar molecules which coat the HIV Env spike expressed on the surface of viral particles. (woofahs.com)
  • In these studies, bNAb resistance emerged in nearly all treated participants who received monotherapy, but in two notable cases 4 the repeated administration of a combination of two bNAbs in the setting of viremia maintained viral suppression for 3 months without development of resistance to either antibody. (nature.com)
  • Given that, bNAbs are ideal for providing sterilizing immunity and are the goal of current HIV-1 vaccine efforts, these data offer insight on how HIV-1 may occlude these vulnerable epitopes from the host immune response. (bvsalud.org)
  • The pretriggered (State-1) conformation of the mature (cleaved) Env is targeted by broadly neutralizing antibodies (bNAbs), which are inefficiently elicited compared with poorly neutralizing antibodies (pNAbs). (bvsalud.org)
  • Approximately 20-30% of HIV-1 infected individuals generate antibodies capable of neutralizing diverse heterologous viral strains (broadly neutralizing antibodies or bNAbs). (washington.edu)
  • These antibodies were called broadly neutralizing antibodies (bNAbs) Dovitinib Dilactic acid [4]. (ecolowood.com)
  • This review summarizes current literature on bNAbs, which suggests new options for anti-HIV-1 vaccine design. (ecolowood.com)
  • He conducted postdoctoral research in the Department of Immunology at St. Jude Children's Research Hospital in Memphis, Tennessee before being appointed research associate at the Duke Human Vaccine Institute, Duke University School of Medicine in Durham, North Carolia, where his activity focused primarily on HIV vaccine development. (nih.gov)
  • A very exciting project on broadly neutralizing antibodies with influenza virus has revealed novel epitopes that are of great value for structure-assisted vaccine development. (scripps.edu)
  • Thus far, a subtype B IMC backbone expressing Renilla luciferase (LucR), and into which the ectodomain of heterologous env coding sequences can be expressed has been successfully developed but as execution of HIV-1 vaccine efficacy trials shifts increasingly to non-subtype B epidemics (Southern African and Southeast Asia), non-subtype B HIV-1 reagents are needed to support vaccine development. (plos.org)
  • The enormous genetic diversity of HIV presents a major problem for vaccine development. (aphios.com)
  • Structure of a transmission blocking antibody in complex with Outer surface protein A from the Lyme disease spirochete, Borreliella burgdorferi. (umassmed.edu)
  • Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. (ebiotrade.com)
  • have unique characteristics which include high levels of somatic mutations and unusually very long variable loops that penetrate through the glycan shield of HIV-1 Env to Dovitinib Dilactic acid contact the protein surface. (ecolowood.com)
  • Our study revealed that a class of vaccine-induced human antibodies potently blocks HIV-1 Env-Galcer binding by perturbing the HIV-1 Env conformation. (duke.edu)
  • Human aCL antibodies cause placental necrosis in BALB/c mice. (medscape.com)
  • Studies will encompass primarily human and non-human primate specimens, as well as murine models, and will use multiple virus models, including HIV, flaviviruses, influenza virus, herpesviruses and betacoronaviruses. (nih.gov)
  • A Prevalent Focused Human Antibody Response to the Influenza Virus Hemagglutinin Head Interface. (duke.edu)
  • The team found that instead of binding to small fragments of the virus-like mouse antibodies do-human antibodies that neutralized the virus bound to a complex structure that was only present on a completely assembled dengue virus. (newstrackindia.com)
  • CD4 is a receptor for the human immunodeficiency virus (HIV). (thermofisher.com)
  • Applications Tested: This RPA-T4 antibody has been pre-titrated and tested by flow cytometric analysis of normal human peripheral blood cells. (thermofisher.com)
  • Applications Tested: This MBSA43 antibody has been pre-titrated and tested by flow cytometric analysis of normal human peripheral blood cells. (thermofisher.com)
  • The human monoclonal antibody (MAb) 2909 recognizes a QNE present on the oligomeric Env spike present on the surface of HIV-1 SF162 virions (8). (woofahs.com)
  • The Overbaugh lab (Human Biology) sought to better understand how the mother's antibody response affects the viruses that are transmitted to infants using samples obtained 20 years ago in a longitudinal HIV study from Kenya, before effective antiretroviral therapies were developed. (fredhutch.org)
  • Human monoclonal antibodies are characterized to study the humoral immune response in these disorders. (umassmed.edu)
  • Not only do we generate new human monoclonal antibodies for our studies, but also for a large number of laboratories throughout the world for research on infectious diseases, cancer and autoimmune disease. (umassmed.edu)
  • We collaborate with Drs. Greiner, Brehm and Luban here at UMMS and Dr. Leonard Schultz at Jackson Laboratories on humanized mouse models for the generation of human monoclonal antibodies and as models for passive immunotherapy for bacterial or viral infections. (umassmed.edu)
  • The laboratory has also been involved in pharmacokinetic and pharmacodynamic studies of IgG and IgA human monoclonal antibodies, in several bacterial and viral infections. (umassmed.edu)
  • Enterotoxigenic Escherichia coli,, Bordetella pertussis, Klebsiella pneumonia), she is also inventor of two human monoclonal antibodies against Staphylococcus aureus and Pseudomonas aeruginosa. (umassmed.edu)
  • Since it was identified in 1984 as the cause of Acquired Immune Deficiency Syndrome (AIDS), the human immunodeficiency virus (HIV) has infected more than 80 million people and been responsible for some 40 million deaths worldwide, according to the World Health Organization (WHO). (technologynetworks.com)
  • The human immunodeficiency virus-1 (HIV-1) has the ability to evade the adaptive immune response due to high mutation rates. (ecolowood.com)
  • The human being immunodeficiency disease type 1 (HIV-1), which causes the acquired immunodeficiency syndrome (AIDS), was found out over 30 years ago. (ecolowood.com)
  • Expenditures on tuberculosis treatment may increase over the next few years because of high morbidity rates among people infected with the human immunodeficiency virus (HIV), the homeless, the foreign-born, the elderly, and various minority groups. (cdc.gov)
  • The "capture antibody" is usually binding the alpha subunit of FSH, while the "detection antibody" is always binding within the FSH-specific beta-subunit. (medscape.com)
  • Using a high-throughput functional screen, the investigators cultured and screened individual B-cells for the production of antibodies with the capacity to neutralize an HIV-1 variant. (fredhutch.org)
  • This discovery will certainly open new research avenues towards the characterization, control and eradication of the latent HIV reservoir. (europa.eu)
  • Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells. (duke.edu)
  • A safe and potent vaccine against HIV-1 could limit the spread of HIV-1 and consequently eradicate the disease. (ecolowood.com)
  • Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy. (harvard.edu)
  • In the era of highly active antiretroviral therapy (HAART), people are living longer with HIV/AIDS, and it has become increasingly important to understand the relation between current HIV status and risky sexual behaviour. (bmj.com)
  • The introduction of antiretroviral therapy (ART) for HIV treatment and antiretroviral drugs for pre-exposure prophylaxis (PrEP), including long-acting formulations, has changed the trajectory of the HIV epidemic. (nih.gov)
  • While antiretroviral therapy helps keep HIV in check, patients must stay on their medication to prevent the development of AIDS. (technologynetworks.com)
  • In the HIV field, Dr. Bonsignori isolated multiple broadly neutralizing antibody B cell lineages from chronically HIV-1 infected individuals and characterized antibody/virus co-evolution to rationally select immunogen candidates for sequential vaccination schemes. (nih.gov)
  • Dr. Bonsignori developed a high-throughput memory B cell culture system for the functional screening of memory B cells at the single-cell level and conceptualized a novel framework for steering the immune response through immunogen design based on the probability of individual mutations and their effect on antibody effector functions. (nih.gov)
  • Previous experiments in chimpanzees showed that good humoral and cellular responses could be induced with an inactivated, whole HIV immunogen. (aphios.com)
  • However, the MAb 17B itself did not block Env-Galcer binding, suggesting that the C1 antibody-induced gp120 conformational changes resulted in alteration in a Galcer binding site distant from the CD4i 17B MAb binding site. (duke.edu)
  • Structural basis of coreceptor recognition by HIV-1 envelope spike. (harvard.edu)
  • To investigate the structural effect of both increasing the peptide length and of introducing helix-promoting constraints in the 4E10 epitope, we have determined crystal structures of Fab 4E10 bound to an optimized peptide epitope (NWFDITNWLWYIKKKK-NH(2)), an Aib-constrained peptide epitope (NWFDITNAibLWRR-NH(2)), and a thioether-linked peptide (NWFCITOWLWKKKK-NH(2)) to resolutions of 1.7 A, 2.1 A, and 2.2 A, respectively. (rcsb.org)
  • Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies. (duke.edu)
  • Underserved areas and populations in high-income countries also experience social and structural obstacles to accessing otherwise widely available services, shown by the HIV epidemic in the USA and former Soviet Union countries. (advfn.com)
  • These methods inactivate HIV without causing major structural and physical damage to the virion, including gp120. (aphios.com)
  • Thus, during the later part of the study (2003-2004), entire length of the P. jirovecii Msg, and analyzed their additional serial convalescent-phase serum specimens reactivity with serum antibodies in different populations were drawn every 1-2 weeks for 6 weeks from patients by Western blot (WB) and ELISA ( 17 , 18 ). (cdc.gov)
  • Natural antibodies (Abs) can target host glycans on the surface of pathogens. (duke.edu)
  • Several functions have been proposed for natural antibodies, including a first-line role in the defense against infections, a scavenger-like activity to apoptosis by-products and a turn-off, regulative role in the maintenance of immune homeostasis [ 7 , 14 ]. (biomedcentral.com)
  • The investigators first isolated memory B-cells -immune cells that produce antibodies- from the sample collected from the mother at 31-weeks of pregnancy. (fredhutch.org)
  • These immune assays will be advanced by the development of standardized viral stocks, such as HIV-1 infectious molecular clones (IMC), that i) express a reporter gene, ii) are representative of globally diverse subtypes and iii) are engineered to easily exchange envelope (env) genes for expression of sequences of interest. (plos.org)
  • The Evolving HIV-1 Epidemic in Warao Amerindians Is Dominated by an Extremely High Frequency of CXCR4-Utilizing Strains. (harvard.edu)
  • CXCR4-using HIV variants in a cohort of Black men who have sex with men: HIV Prevention Trials Network 061. (harvard.edu)
  • Humoral Immune Pressure Selects for HIV-1 CXC-chemokine Receptor 4-using Variants. (harvard.edu)
  • It is well-documented that infants who get infected in an MTCT setting only acquire a few of the maternal HIV variants. (fredhutch.org)
  • To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 Å resolution of the broadly neutralizing antibody b12 in complex with gp120. (elsevierpure.com)
  • We have moved on to nanobody discovery for broadly neutralizing antibodies against all variants of concern and interest. (umassmed.edu)
  • The utility and technical advantages of synthetic nucleic acid platforms (SNAP), including their efficacy, safety, speed of development, and ease of vaccine manufacture, were revealed during the COVID-19 pandemic, thus instilling hope that these technologies can be leveraged for the development of an effective HIV vaccine and broadly neutralizing antibody (bNAb) delivery. (nih.gov)
  • Scientists have spent years trying to develop an effective HIV vaccine, but none have proven successful. (technologynetworks.com)
  • If we can identify which epitopes are 'immunodominant' - the ones that elicit the strongest immune system response to the virus - then we may have the essential ingredients for the long-sought recipe to make an effective HIV vaccine," explains Sadegh-Nasseri. (technologynetworks.com)
  • The secondary endpoints were changes in anti-PGT121 antibody titers and CD4 + T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. (nature.com)
  • Major advances in HIV/AIDS treatment regimens have fundamentally altered the natural history of the disease and sharply reduced HIV-related morbidity and mortality in countries where such treatments are accessible. (europa.eu)
  • Studies have shown it to be effective in treating HIV/AIDS. (nbc4i.com)
  • The persistence of HIV in treated patients results from the establishment of a viral reservoir insensitive to ART and poorly visible to the immune system. (europa.eu)
  • The purpose of this Funding Opportunity Announcement (FOA) is to foster interdisciplinary basic, translational, and clinical research that will define Natural Killer (NK) cell functions and interactions with other components of the innate and adaptive immune system affecting the potency and durability of HIV-1-specific immunity, including vaccine efficacy, reservoir size, reactivation or post-treatment control. (nih.gov)
  • Current research strategies aiming to prevent, control or eradicate HIV emphasize the adaptive arm of the immune system, harnessing effector functions of cytotoxic T cells, helper T cells, B cells and antibodies to attack HIV and HIV-infected cells. (nih.gov)
  • Historically, NK cells have been considered part of the innate immune system, recognizing and eliminating virus-infected or tumor cells either directly by release of cytotoxic granules or indirectly by cytokine release and facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). (nih.gov)
  • One area in which we and others have already made an impact is in understanding how HIV-1 is able to evade the humoral immune system. (nih.gov)
  • Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. (nature.com)
  • Much of our recent work is focused on HIV-1 and influenza viruses. (scripps.edu)
  • The RPA-T4 antibody binds to the D1 domain of CD4 (CDR1 and CDR3 epitopes) and can block HIV gp120 binding and inhibit syncytia formation. (biolegend.com)
  • UNLABELLED: Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated to be a receptor for HIV-1 envelope (Env) interactions with mucosal epithelial cells. (duke.edu)
  • To study antibody modulation of HIV-1 Env-Galcer interactions, we used Galcer-containing liposomes to assess whether natural- and vaccine-induced monoclonal antibodies can block HIV-1 Env binding to Galcer. (duke.edu)
  • Our combined studies reveal that 2G12 is capable of binding both the D1 and D3 arms of the Man(9)GIcNAC(2) moiety, which would provide more flexibility to make the required multivalent interactions between the antibody and the gp120 oligomannose cluster than thought previously. (boku.ac.at)
  • We further show that lectin-glycan interactions can also expose these epitopes. (bvsalud.org)
  • Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. (elsevierpure.com)
  • Epitopes of SARS-CoV spikeproteins were mapped, using Qβ and evaluated for potential antibody neutralizing determinants critically important in the development of an efficacious vaccine candidate. (alliedacademies.org)
  • We propose that the V2 and C2 regions of AE-Env gp120 contain the major determinants of viral resistance to CD4bs antibodies. (biomedcentral.com)
  • Analysis of recognition of the CD4 supersite in 14 donors suggest that steric access to the CD4 supersite is a primary physical constraint limiting antibody recognition (Zhou 2015 Cell 161, 1280-1292). (nih.gov)
  • One functional constraint involves receptor binding - with the site on HIV-1 Env involved in binding the CD4 receptor providing a "supersite of vulnerability. (nih.gov)
  • However, many cross-reactive conserved epitopes are often occluded on virus particles, contributing to the evasion of humoral immunity. (bvsalud.org)
  • These and other studies - including the determination of the crystal structure of the entire spike ectodomain (Pancera 2014 Nature 514, 455-461) and the determination of the crystal structure of fully glycosylated envelope trimers (Stewart-Jones 2016 Cell 165, 813-826) - have led to an understanding of the molecular trickery that protects HIV-1 from the humoral immune response. (nih.gov)