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https://www.readbyqxmd.com/read/29226015/conserved-hiv-epitopes-for-an-effective-hiv-vaccine
#1
Bikash Sahay, Cuong Q Nguyen, Janet K Yamamoto
Despite major advances in antiretroviral therapy against HIV-1, an effective HIV vaccine is urgently required to reduce the number of new cases of HIV infections in the world. Vaccines are the ultimate tool in the medical arsenal to control and prevent the spread of infectious diseases such as HIV/AIDS. Several failed phase-IIb to -III clinical vaccine trials against HIV-1 in the past generated a plethora of information that could be used for better designing of an effective HIV vaccine in the future. Most of the tested vaccine candidates produced strong humoral responses against the HIV proteins; however, failed to protect due to: 1) the low levels and the narrow breadth of the HIV-1 neutralizing antibodies and the HIV-specific antibody-dependent Fc-mediated effector activities, 2) the low levels and the poor quality of the anti-HIV T-cell responses, and 3) the excessive responses to immunodominant non-protective HIV epitopes, which in some cases blocked the protective immunity and/or enhanced HIV infection...
August 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/29226013/novel-therapeutic-approach-for-inhibition-of-hiv-1-using-cell-penetrating-peptide-and-bacterial-toxins
#2
Steven Samuels, Zainab Alwan, Marceline Egnin, Jessie Jaynes, Terry D Connell, Gregory C Bernard, Toufic Nashar
Despite advancements in our understanding of HIV-1 pathogenesis, critical virus components for immunity, vaccines trials, and drugs development, challenges remain in the fight against HIV-1. Of great importance is the inhibitory function of microbicidal cell penetrating peptides and bacterial toxins that interfere with production and neutralize infection of HIV-1 particles. We demonstrate that the neutralizing activity of a cationic 18 amino acids peptide, is similar to a broadly neutralizing human antibody, and inhibits production of two HIV-1 strains in human cell lines...
October 2017: Journal of AIDS & Clinical Research
https://www.readbyqxmd.com/read/29222332/stabilization-of-the-gp120-v3-loop-through-hydrophobic-interactions-reduces-the-immunodominant-v3-directed-non-neutralizing-response-to-hiv-1-envelope-trimers
#3
Steven W de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A Burger, Patricia van der Woude, Anna Schorcht, Edith E Schermer, Marit J van Gils, Celia C LaBranche, David C Montefiori, Ian A Wilson, John P Moore, Andrew B Ward, Rogier W Sanders
To provide protective immunity against circulating primary HIV-1 strains, a vaccine most likely has to induce broadly neutralizing antibodies (bNAbs) to the HIV-1 envelope (Env) glycoprotein spike. Recombinant Env trimers such as the prototype BG505 SOSIP.664 that closely mimic the native Env spike can induce autologous neutralizing antibodies (NAbs) against relatively resistant (tier-2) primary viruses. Ideally, Env immunogens should present bNAb epitopes, but limit the presentation of immunodominant non-NAb epitopes that might induce off-target and potentially interfering responses...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29218117/basis-and-statistical-design-of-the-passive-hiv-1-antibody-mediated-prevention-amp-test-of-concept-efficacy-trials
#4
Peter B Gilbert, Michal Juraska, Allan C deCamp, Shelly Karuna, Srilatha Edupuganti, Nyaradzo Mgodi, Deborah J Donnell, Carter Bentley, Nirupama Sista, Philip Andrew, Abby Isaacs, Yunda Huang, Lily Zhang, Edmund Capparelli, Nidhi Kochar, Jing Wang, Susan H Eshleman, Kenneth H Mayer, Craig A Magaret, John Hural, James G Kublin, Glenda Gray, David C Montefiori, Margarita M Gomez, David N Burns, Julie McElrath, Julie Ledgerwood, Barney S Graham, John R Mascola, Myron Cohen, Lawrence Corey
Background: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. Methods: The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa...
January 2017: Statistical Communications in Infectious Diseases
https://www.readbyqxmd.com/read/29209323/non-neutralizing-antibodies-directed-against-hiv-and-their-functions
#5
REVIEW
Luzia M Mayr, Bin Su, Christiane Moog
B cells produce a plethora of anti-HIV antibodies (Abs) but only few of them exhibit neutralizing activity. This was long considered a profound limitation for the enforcement of humoral immune responses against HIV-1 infection, especially since these neutralizing Abs (nAbs) are extremely difficult to induce. However, increasing evidence shows that additional non-neutralizing Abs play a significant role in decreasing the viral load, leading to partial and sometimes even total protection. Mechanisms suspected to participate in protection are numerous...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29194123/anti-hiv-1-antibody-dependent-cellular-cytotoxicity-is-there-more-to-antibodies-than-neutralization
#6
Wen Shi Lee, Stephen J Kent
PURPOSE OF REVIEW: An increasing body of evidence suggests that nonneutralizing Fc effector functions including antibody-dependent cellular cytotoxicity (ADCC) contribute to protection against HIV-1 acquisition. We discuss recent advances in anti-HIV-1 ADCC research with a particular focus on ADCC mediated by Env-specific antibodies in vitro and in vivo, the curative potential of HIV-1-specific ADCC antibodies and the mechanisms of HIV-1 resistance to ADCC. RECENT FINDINGS: ADCC activities of broadly neutralizing and nonneutralizing monoclonal antibody panels were recently characterized in vitro against several lab-adapted and primary isolates of HIV-1...
November 30, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29187855/cd4-binding-site-directed-cross-neutralizing-scfv-monoclonals-from-hiv-1-subtype-c-infected-indian-children
#7
Sanjeev Kumar, Rajesh Kumar, Lubina Khan, Muzamil Ashraf Makhdoomi, Ramachandran Thiruvengadam, Madhav Mohata, Mudit Agarwal, Rakesh Lodha, Sushil Kumar Kabra, Subrata Sinha, Kalpana Luthra
Progression of human immunodeficiency virus type-1 (HIV-1) infection in children is faster than adults. HIV-1 subtype C is responsible for more than 50% of the infections globally and more than 90% infections in India. To date, there is no effective vaccine against HIV-1. Recent animal studies and human Phase I trials showed promising results of the protective effect of anti-HIV-1 broadly neutralizing antibodies (bnAbs). Interaction between CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein and CD4 receptor on the host immune cells is the primary event leading to HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29187598/epitope-focused-immunogens-against-the-cd4-binding-site-of-hiv-1-envelope-protein-induce-neutralizing-antibodies-against-auto-and-heterologous-viruses
#8
Hua Wang, Xiangjun Chen, Dianhong Wang, Chen Yao, Qian Wang, Jiayu Xie, Xuanling Shi, Ye Xiang, Wanli Liu, Linqi Zhang
Recent discoveries of broadly neutralizing antibodies (bnAbs) in HIV-1-infected individuals have led to the identification of several major ″vulnerable sites″ on the HIV-1 envelope (Env) glycoprotein. These sites have provided precise targets for HIV-1 vaccine development, but identifying and utilizing many of these targets remains technically challenging. Using a yeast surface display-based approach, we sought to identify epitope-focused antigenic domains (EADs) containing one of the ″vulnerable sites″, the CD4-binding site (CD4bs), through screening and selection of a combinatorial antigen library of the HIV-1 Env glycoprotein with the CD4bs bnAb VRC01...
November 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29175625/increased-surface-expression-of-hiv-1-envelope-is-associated-with-improved-antibody-response-in-vaccinia-prime-protein-boost-immunization
#9
Michael J Hogan, Angela Conde-Motter, Andrea P O Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C LaBranche, David C Montefiori, Shiu-Lok Hu, James A Hoxie, Drew Weissman
HIV-1 envelope (Env)-based vaccines have so far largely failed to induce antibodies that prevent HIV-1 infection. One factor proposed to limit the immunogenicity of cell-associated Env is its low level of expression on the cell surface, restricting accessibility to antibodies. Using a vaccinia prime/protein boost protocol in mice, we explored the immunologic effects of mutations in the Env cytoplasmic tail (CT) that increased surface expression, including partial truncation and ablation of a tyrosine-dependent endocytosis motif...
November 22, 2017: Virology
https://www.readbyqxmd.com/read/29173180/the-neutralizing-antibody-response-to-the-hiv-1-env-protein
#10
Penny L Moore
BACKGROUND: A vaccine able to elicit broadly neutralizing antibodies capable of blocking infection by global viruses has not been achieved, and remains a key public health challenge. OBJECTIVE: During infection, a robust strain-specific neutralizing response develops in most people, but only a subset of infected people develop broadly neutralizing antibodies. Understanding how and why these broadly neutralizing antibodies develop has been a focus of the HIV-1 vaccine field for many years, and has generated extraordinary insights into the neutralizing response to HIV-1 infection...
November 24, 2017: Current HIV Research
https://www.readbyqxmd.com/read/29170914/immunological-and-virological-characteristics-of-human-immunodeficiency-virus-type-1-superinfection-implications-in-vaccine-design
#11
REVIEW
Yang Gao, Wen Tian, Xiaoxu Han, Feng Gao
Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection...
November 23, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/29170366/initiation-of-hiv-neutralizing-b-cell-lineages-with-sequential-envelope-immunizations
#12
Wilton B Williams, Jinsong Zhang, Chuancang Jiang, Nathan I Nicely, Daniela Fera, Kan Luo, M Anthony Moody, Hua-Xin Liao, S Munir Alam, Thomas B Kepler, Akshaya Ramesh, Kevin Wiehe, James A Holland, Todd Bradley, Nathan Vandergrift, Kevin O Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori, David C Montefiori, Mark Louder, Amanda Eaton, Sampa Santra, Richard Scearce, Laura Sutherland, Amanda Newman, Hilary Bouton-Verville, Cindy Bowman, Howard Bomze, Feng Gao, Dawn J Marshall, John F Whitesides, Xiaoyan Nie, Garnett Kelsoe, Steven G Reed, Christopher B Fox, Kim Clary, Marguerite Koutsoukos, David Franco, John R Mascola, Stephen C Harrison, Barton F Haynes, Laurent Verkoczy
A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29166592/hiv-envelope-glycoform-heterogeneity-and-localized-diversity-govern-the-initiation-and-maturation-of-a-v2-apex-broadly-neutralizing-antibody-lineage
#13
Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B Ward, Ian A Wilson, Dennis R Burton, Davey Smith, Sergei L Kosakovsky Pond, Pascal Poignard
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166578/glycans-function-as-anchors-for-antibodies-and-help-drive-hiv-broadly-neutralizing-antibody-development
#14
Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S Shivatare, Bryan Briney, James E Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R Burton
No abstract text is available yet for this article.
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29163465/b-cell-activating-factor-and-the-b-cell-compartment-in-hiv-siv-infection
#15
REVIEW
Gwenoline Borhis, Maria Trovato, Nada Chaoul, Hany M Ibrahim, Yolande Richard
With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162799/structure-based-design-of-native-like-hiv-1-envelope-trimers-to-silence-non-neutralizing-epitopes-and-eliminate-cd4-binding
#16
Daniel W Kulp, Jon M Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R Willis, Michael Kubitz, Yumiko Adachi, Samantha M Reiss, Mia Shin, Natalia de Val, Andrew B Ward, Shane Crotty, Dennis R Burton, William R Schief
Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antigens. However, first generation native-like trimers expose epitopes for non-neutralizing antibodies (non-nAbs), which may hinder bnAb induction. We here employ computational and structure-guided design to develop improved native-like trimers that reduce exposure of non-nAb epitopes in the V3-loop and trimer base, minimize both CD4 reactivity and CD4-induced non-nAb epitope exposure, and increase thermal stability while maintaining bnAb antigenicity...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162391/impact-of-hiv-1-envelope-conformation-on-adcc-responses
#17
REVIEW
Jonathan Richard, Jérémie Prévost, Nirmin Alsahafi, Shilei Ding, Andrés Finzi
HIV-1 envelope glycoproteins (Env) represent the only virus-specific antigen exposed at the surface of infected cells. In its unliganded form, Env from primary viruses samples a 'closed' conformation (State 1), which is preferentially recognized by broadly neutralizing antibodies (bNAbs). CD4 engagement drives Env into an intermediate 'partially open' (State 2) and then into the 'open' CD4-bound conformation (State 3). Emerging evidence suggests a link between Env conformation and Ab-dependent cellular cytotoxicity (ADCC)...
November 18, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#18
Antu K Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K Sharma, Anna-Janina Behrens, Eden P Go, Thomas J Ketas, Anila Yasmeen, Per J Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A Wilson, Rogier W Sanders, Thomas Hassell, Andrew Ward, John P Moore
We describe the properties of BG505 SOSIP.664 HIV-1 envelope glycoprotein trimers produced under current Good Manufacturing Practice (cGMP) conditions. These proteins are the first of a new generation of native-like trimers that are the basis for many structure-guided immunogen development programs aimed at devising how to induce broadly neutralizing antibodies (bNAbs) to HIV-1 by vaccination. The successful translation of this prototype demonstrates the feasibility of producing similar immunogens on an appropriate scale and of an acceptable quality for Phase I experimental medicine clinical trials...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150603/bacterially-derived-synthetic-mimetics-of-mammalian-oligomannose-prime-antibody-responses-that-neutralize-hiv-infectivity
#19
Ralph Pantophlet, Nino Trattnig, Sasha Murrell, Naiomi Lu, Dennis Chau, Caitlin Rempel, Ian A Wilson, Paul Kosma
Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142124/truncating-the-gp41-cytoplasmic-tail-of-siv-decreases-sensitivity-to-neutralizing-antibodies-without-increasing-envelope-content-of-virions
#20
Ellen White, Fan Wu, Elena Chertova, Julian Bess, James D Roser, Jeffrey D Lifson, Vanessa M Hirsch
An incomplete understanding of native HIV and SIV envelope glycoprotein (Env) impedes the development of structural models of Env and vaccine design. This shortcoming is due in part to the low number of Env trimers on virus particles. For SIV, this low expression can be counteracted by truncating the cytoplasmic tail (CT) of Env. CT truncation has been shown to increase Env incorporation into the virion and is commonly used in vaccine and imaging studies, but its effects on viral antigenicity have not been fully elucidated...
November 15, 2017: Journal of Virology
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