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
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.. ...
Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities, especially for multiantibody deliveries, long infusion times, and production issues could limit the use of these bNAbs when deployed, globally affecting their potential application. Here, we describe an approach utilizing synthetic DNA-encoded monoclonal antibodies (dmAbs) for direct in vivo production of prespecified neutralizing activity. We designed 16 different bNAbs as dmAb cassettes and studied their activity in small and large animals. Sera from animals administered dmAbs neutralized multiple HIV-1 isolates with activity similar to that of their parental recombinant mAbs. Delivery of multiple dmAbs to a single animal led to increased neutralization breadth. Two ...
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. ...
Compare & find the top performing anti-Mouse (Murine) Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like antibody for Western Blotting (WB).
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. ...
An antibody with high neutralising potency against SARS-CoV-2 that binds to the NTD of the Spike protein has been identified by a team researching COVID-19.
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 ...
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. ...
Rational immunogen design is an increasingly promising approach for development of an effective human immunodeficiency virus-1 (HIV-1) vaccine. The recent discovery of many new and potent broadly neutralizing antibodies (bnAbs) has helped define conserved sites of vulnerability on the HIV-1 envelope (Env) glycoprotein (gp) complex that mediates viral entry into cells (refs. 1⇓⇓⇓⇓-6 and reviewed in refs. 7⇓⇓⇓-11). Passive immunization studies show that sterilizing immunity can be achieved if sufficient amounts of bnAbs are present before virus challenge in macaques (12⇓⇓⇓-16). Hence, intensive efforts are ongoing to design immunogens capable of re-eliciting these types of bnAbs by vaccination.. The major difficulty in mounting an effective antibody response against HIV-1 resides in the multiple evasion strategies that have evolved in Env. An error-prone reverse transcriptase drives a high degree of Env sequence diversity (17⇓-19). The few conserved regions of Env are ...
A new kind of antibody targets a feature shared by proteins thought to cause the most damage in Alzheimers disease, Parkinsons disease, and related conditions
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 ...
With ,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. Approximately 20-30% of HIV-1 infected individuals generate antibodies capable of neutralizing diverse heterologous viral strains (broadly neutralizing antibodies or bNAbs). Because they protect from experimental infection, it is thought that bNAbs will be an important part of an HIV-1 vaccine. 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. 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.. One of the first critical steps in an effective antibody response is the recognition of a foreign antigen by a membrane ...
With ,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. Approximately 20-30% of HIV-1 infected individuals generate antibodies capable of neutralizing diverse heterologous viral strains (broadly neutralizing antibodies or bNAbs). Because they protect from experimental infection, it is thought that bNAbs will be an important part of an HIV-1 vaccine. 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. 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.. One of the first critical steps in an effective antibody response is the recognition of a foreign antigen by a membrane ...
With ,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. Approximately 20-30% of HIV-1 infected individuals generate antibodies capable of neutralizing diverse heterologous viral strains (broadly neutralizing antibodies or bNAbs). Because they protect from experimental infection, it is thought that bNAbs will be an important part of an HIV-1 vaccine. 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. 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.. One of the first critical steps in an effective antibody response is the recognition of a foreign antigen by a membrane ...
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 ...
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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 ...
DESCRIPTION (provided by applicant): The HIV-1 epidemic has resulted in ~2.7 million new infections in 2007 for a total of ~33 million people living with HIV/AIDS. Clinical trials have shown that HIV-1 infection cannot be prevented by immunization with monomeric recombinant forms of viral envelope (Env) proteins. However, it is clear that the HIV-1 Env contains epitopes that can induce neutralizing antibodies and that such antibodies can protect primates from infection. The HIV-1 Env is a transmembrane glycoprotein. Both the external subunit (gp120) and the membrane- proximal external region of Env (located within the gp41 subunit) contain epitopes that are the target of broadly neutralizing monoclonal antibodies (mAbs) isolated from infected patients. Considerable effort has been devoted to creating soluble forms of the Env trimer. The improvements in immunogenicity of these molecules relative to monomeric gp120 are limited at best. Another approach to creating improved Env-based immunogens is ...
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 ...
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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. ...
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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. ...
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 ...
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, ...
Anti-PDCD1 / CD279 / PD-1 Antibody (clone 4E5) , Mouse Anti Human Monoclonal Antibody validated in WB, IHC-P, IF, Flo (ALS17346), Abgent
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