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HIV neutralizing antibody

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https://www.readbyqxmd.com/read/29040829/soybean-derived-bowman-birk-inhibitor-bbi-blocks-hiv-entry-into-macrophages
#1
Tong-Cui Ma, Le Guo, Run-Hong Zhou, Xu Wang, Jin-Biao Liu, Jie-Liang Li, Yu Zhou, Wei Hou, Wen-Zhe Ho
Bowman-Birk inhibitor (BBI) is a soybean-derived protease inhibitor that has anti-inflammation and anti-HIV effect. Here, we further investigated the anti-HIV action of BBI in macrophages, focusing on its effect on viral entry. We found that BBI could significantly block HIV entry into macrophages. Investigation of the mechanism(s) of the BBI action on HIV inhibition showed that BBI down-regulated the expression of CD4 receptor (as much as 80%) and induced the production of the CC chemokines (up to 60 folds at protein level) in macrophages...
October 14, 2017: Virology
https://www.readbyqxmd.com/read/29035947/cross-reactivity-of-hiv-vaccine-responses-and-the-microbiome
#2
Wilton B Williams, Qifeng Han, Barton F Haynes
PURPOSE OF REVIEW: A successful HIV-type 1 (HIV-1) vaccine will require immunogens that induce protective immune responses. However, recent studies suggest that the response to HIV-1 and perhaps other viruses may be altered by immune system exposure to intestinal microbiota-antigens. This review will discuss select aspects of these studies. RECENT FINDINGS: Naïve CD4 T and B cell repertoires can be imprinted by intestinal microbiota-antigens to respond to virus epitopes prior to virus infection...
October 14, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29029583/new-generation-high-potency-and-designer-antibodies-role-in-hiv-1-treatment
#3
Lucio Gama, Richard A Koup
Broadly neutralizing antibodies (bNAbs) have been evaluated as promising agents in the fight against infectious diseases. HIV-1-specific bNAbs, in particular, have been tested in both preventive and therapeutic modalities. Multiple bNAbs have been isolated, characterized, and assessed in vitro and in vivo, but no single antibody appears to possess the breadth and potency that may be needed if it is to be used in the treatment of HIV-1 infection. With the technological advances of the past decades, novel and more effective bNAbs have been identified or engineered for higher neutralizing potency, greater breadth, and increased serum half-life...
October 13, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29028655/potency-of-hiv-2-specific-antibodies-increase-in-direct-association-with-loss-of-memory-b-cells
#4
Cheila Rocha, Joana Duarte, Pedro Borrego, Rita Calado, José M Marcelino, Rita Tendeiro, Emília Valadas, Ana E Sousa, Nuno Taveira
: Potent HIV neutralizing antibodies are critical for vaccination and viral reservoir control. High levels of neutralizing antibodies characterize HIV-2 infection, a naturally-occurring model of attenuated HIV disease with low to undectable viremia. We found that HIV-2-specific antibody potency increased in direct association with the loss of both switched and unswitched memory B-cells in untreated HIV-2 infection. Thus, HIV antibody affinity maturation is linked to memory B-cell exhaustion even in reduced viremia settings...
October 12, 2017: AIDS
https://www.readbyqxmd.com/read/29023549/supraphysiologic-control-over-hiv-1-replication-mediated-by-cd8-t-cells-expressing-a-re-engineered-cd4-based-chimeric-antigen-receptor
#5
Rachel S Leibman, Max W Richardson, Christoph T Ellebrecht, Colby R Maldini, Joshua A Glover, Anthony J Secreto, Irina Kulikovskaya, Simon F Lacey, Sarah R Akkina, Yanjie Yi, Farida Shaheen, Jianbin Wang, Keith A Dufendach, Michael C Holmes, Ronald G Collman, Aimee S Payne, James L Riley
HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29021394/hiv-1-gp120-protein-and-mvagp140-boost-immunogens-increase-immunogenicity-of-a-dna-mva-hiv-1-vaccine
#6
Xiaoying Shen, Rahul Basu, Sheetal Sawant, David Beaumont, Sue Fen Kwa, Celia LaBranche, Kelly E Seaton, Nicole L Yates, David C Montefiori, Guido Ferrari, Linda S Wyatt, Bernard Moss, S Munir Alam, Barton F Haynes, Georgia D Tomaras, Harriet L Robinson
An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia Ankara (MVA) expressing HIV-1 Env on virus like particles. Here we evaluated whether the addition of a gp120 protein in alum or MVA expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime - MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26 and 40...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29020058/hiv-transmitted-founder-vaccines-elicit-autologous-tier-2-neutralizing-antibodies-for-the-cd4-binding-site
#7
Nathanael P McCurley, Arban Domi, Rahul Basu, Kevin O Saunders, Celia C LaBranche, David C Montefiori, Barton F Haynes, Harriet L Robinson
Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30)...
2017: PloS One
https://www.readbyqxmd.com/read/29017536/a-strongly-selected-mutation-in-the-hiv-1-genome-is-independent-of-t-cell-responses-and-neutralizing-antibodies
#8
Donglai Liu, Chu Wang, Bhavna Hora, Tao Zuo, Nilu Goonetilleke, Michael K P Liu, Mark Berrong, Guido Ferrari, Andrew J McMichael, Tanmoy Bhattacharya, Alan S Perelson, Feng Gao
BACKGROUND: Mutations rapidly accumulate in the HIV-1 genome after infection. Some of those mutations are selected by host immune responses and often cause viral fitness losses. This study is to investigate whether strongly selected mutations that are not associated with immune responses result in fitness losses. RESULTS: Strongly selected mutations were identified by analyzing 5'-half HIV-1 genome (gag/pol) sequences from longitudinal samples of subject CH0131...
October 10, 2017: Retrovirology
https://www.readbyqxmd.com/read/28994411/x-ray-and-em-structures-of-a-natively-glycosylated-hiv-1-envelope-trimer
#9
Harry B Gristick, Haoqing Wang, Pamela J Bjorkman
The structural and biochemical characterization of broadly neutralizing anti-HIV-1 antibodies (bNAbs) has been essential in guiding the design of potential vaccines to prevent infection by HIV-1. While these studies have revealed critical mechanisms by which bNAbs recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env), they have been limited to the visualization of high-mannose glycan forms only, since heterogeneity introduced from the presence of complex glycans makes it difficult to obtain high-resolution structures...
October 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28994384/-follicular-helper-t-cells-and-hiv-united-for-better-and-worse
#10
Angeline Rouers, Raphaël Jeger-Madiot, Arnaud Moris, Stéphanie Graff-Dubois
Follicular helper T cells (Tfh) have been discovered in lymph nodes and, since then, are the focus of very intensive research to understand their origin, differentiation and functions. Tfh interact with B cells in the secondary lymphoid organs leading to B cell differentiation and maturation. Tfh are particularly studied in pathological contexts such as autoimmune diseases and infection by the human immunodeficiency virus (HIV). In the context of HIV infection, broadly neutralizing antibodies have been identified in a few patients...
October 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28983040/broadly-neutralizing-antibodies-to-prevent-hiv-1
#11
Myron S Cohen, Lawrence Corey
No abstract text is available yet for this article.
October 6, 2017: Science
https://www.readbyqxmd.com/read/28982260/immunization-with-clinical-hiv-1-env-proteins-induces-broad-antibody-dependent-cellular-cytotoxicity-adcc-mediating-antibodies-in-a-rabbit-vaccination-model
#12
Ingrid Karlsson, Marie Borggren, Sanne Skov Jensen, Leo Heyndrickx, Guillaume Stewart-Jones, Gabriella Scarlatti, Anders Fomsgaard
The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, e.g., antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone and DNA prime with protein boost...
October 6, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28978939/non-neutralizing-antibodies-targeting-the-v1v2-domain-of-hiv-exhibit-strong-antibody-dependent-cell-mediated-cytotoxic-activity
#13
Luzia M Mayr, Thomas Decoville, Sylvie Schmidt, Géraldine Laumond, Jéromine Klingler, Camille Ducloy, Seiamak Bahram, Susan Zolla-Pazner, Christiane Moog
The development of an effective vaccine against HIV-1 has proven to be challenging. Broadly neutralizing antibodies (bNAbs), whilst exhibiting neutralization breadth and potency, are elicited only in a small subset of infected individuals and have yet to be induced by vaccination. Case-control studies of RV144 identified an inverse correlation of HIV-1 infection risk with antibodies (Abs) to the V1V2 region of gp120 with high antibody-dependent cellular cytotoxicity (ADCC) activity. The neutralizing activity of Abs was not found to contribute to this protective outcome...
October 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28978711/functional-stability-of-hiv-1-envelope-trimer-affects-accessibility-to-broadly-neutralizing-antibodies-at-its-apex
#14
Syna Kuriakose Gift, Daniel P Leaman, Lei Zhang, Arthur S Kim, Michael B Zwick
The trimeric envelope glycoprotein spike (Env) of HIV-1 is the target of vaccine development to elicit broadly neutralizing antibodies (bnAbs). Env trimer instability and heterogeneity in principle make subunit interfaces inconsistent targets for the immune response. Here, we investigate how functional stability of Env relates to neutralization sensitivity to V2 bnAbs and V3 crown antibodies that engage subunit interfaces upon binding to unliganded Env. Env heterogeneity was inferred when antibodies neutralized a mutant Env with a plateau of less than 100% percentage neutralization...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28978475/elicitation-of-neutralizing-antibodies-targeting-the-v2-apex-of-the-hiv-envelope-trimer-in-a-wild-type-animal-model
#15
James E Voss, Raiees Andrabi, Laura E McCoy, Natalia de Val, Roberta P Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N Khan, Fernando Garces, Laura K Pritchard, Richard T Wyatt, Andrew B Ward, Max Crispin, Ian A Wilson, Dennis R Burton
Recent efforts toward HIV vaccine development include the design of immunogens that can engage B cell receptors with the potential to affinity mature into broadly neutralizing antibodies (bnAbs). V2-apex bnAbs, which bind a protein-glycan region on HIV envelope glycoprotein (Env) trimer, are among the most broad and potent described. We show here that a rare "glycan hole" at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bnAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, we immunized wild-type rabbits with soluble trimers adapted from these Envs...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28972148/time-course-negative-stain-electron-microscopy-based-analysis-for-investigating-protein-protein-interactions-at-the-single-molecule-level
#16
Bartek Nogal, Charles A Bowman, Andrew B Ward
Several biophysical approaches are available to study protein-protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein-protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate timescale...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28970835/immunologic-insights-on-the-membrane-proximal-external-region-a-major-human-immunodeficiency-virus-type-1-vaccine-target
#17
REVIEW
Luis M Molinos-Albert, Bonaventura Clotet, Julià Blanco, Jorge Carrillo
Broadly neutralizing antibodies (bNAbs) targeting conserved regions within the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein (Env) can be generated by the human immune system and their elicitation by vaccination will be a key point to protect against the wide range of viral diversity. The membrane proximal external region (MPER) is a highly conserved region within the Env gp41 subunit, plays a major role in membrane fusion and is targeted by naturally induced bNAbs. Therefore, the MPER is considered as an attractive vaccine target...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28969431/intradermal-hiv-1-dna-immunization-using-needle-free-zetajet-sup-tm-sup-injection-followed-by-hiv-modified-vaccinia-virus-ankara-vaccination-is-safe-and-immunogenic-in-mozambican-young-adults-a-phase-i-randomized-controlled-trial
#18
Edna Omar Viegas, Nelson Tembe, Charlotta Nilsson, Bindiya Meggi, Cremildo Maueia, Orvalho Augusto, Richard Stout, Gabriella Scarlatti, Guido Ferrari, Patricia Earl, Britta Wahren, Sören Andersson, Merlin Robb, Nafissa Osman, Gunnel Biberfeld, Ilesh Jani, Eric Sandström
We assessed safety and immunogenicity of HIV-DNA priming using Zetajet<sup>TM</sup>, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0.2mL) of HIV-DNA (3 mg/mL), followed by two boosts of 10<sup>8</sup>pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups...
October 2, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28968970/identification-of-a-novel-hiv-1-neutralizing-antibody-from-a-crf07_bc-infected-chinese-donor
#19
Youxiang Sun, Yuanyuan Qiao, Yuanmei Zhu, Huihui Chong, Yuxian He
The identification of human monoclonal antibodies (mAbs) able to neutralize a broad spectrum of primary HIV-1 isolates is highly important for understanding the immune response of HIV-1 infection and developing vaccines and therapeutics. In this study, we isolated a novel human mAb termed Y498 from a phage display antibody library constructed with the PBMC samples of a CRF07_BC-infected Chinese donor whose sera exhibited broadly neutralizing activity. Y498 cross-reacted with diverse Env antigens and neutralized 30% of 70 tested HIV-1 isolates...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968759/safety-and-immunogenicity-of-pennvax%C3%A2-g-dna-prime-administered-by-biojector%C3%A2-2000-or-cellectra%C3%A2-electroporation-device-with-modified-vaccinia-ankara-cmdr-boost
#20
Julie A Ake, Alexandra Schuetz, Poonam Pegu, Lindsay Wieczorek, Michael A Eller, Hannah Kibuuka, Fredrick Sawe, Leonard Maboko, Victoria Polonis, Nicos Karasavva, David Weiner, Arthur Sekiziyivu, Josphat Kosgei, Marco Missanga, Arne Kroidl, Philipp Mann, Silvia Ratto-Kim, Leigh Anne Eller, Patricia Earl, Bernard Moss, Julie Dorsey-Spitz, Mark Milazzo, G Laissa Ouedraogo, Farrukh Rizvi, Jian Yan, Amir S Khan, Sheila Peel, Niranjan Y Sardesai, Nelson L Michael, Viseth Ngauy, Mary Marovich, Merlin L Robb
Background: We report the first-in-human safety and immunogenicity evaluation of PENNVAX®-G DNA/ MVA-CMDR prime-boost HIV vaccine, with intramuscular DNA delivery by either Biojector® 2000 needle free injection system (Biojector) or by CELLECTRA® electroporation device. Methods: Healthy, HIV-uninfected adults were randomized to receive 4 mg PENNVAX®-G DNA delivered IM by Biojector or electroporation at baseline and week 4 followed by IM injection of 108 pfu MVA-CMDR at week 12 and 24...
September 2, 2017: Journal of Infectious Diseases
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