keyword
MENU ▼
Read by QxMD icon Read
search

Hiv and broadly neutralizing antibody

keyword
https://www.readbyqxmd.com/read/28933684/screening-of-primary-gp120-immunogens-to-formulate-the-next-generation-polyvalent-dna-prime-protein-boost-hiv-1-vaccines
#1
Shixia Wang, Te-Hui Wu, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul Clapham, James Arthos, David Montefiori, Shan Lu
Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28931655/protection-against-a-mixed-shiv-challenge-by-a-broadly-neutralizing-antibody-cocktail
#2
Boris Julg, Po-Ting Liu, Kshitij Wagh, William M Fischer, Peter Abbink, Noe B Mercado, James B Whitney, Joseph P Nkolola, Katherine McMahan, Lawrence J Tartaglia, Erica N Borducchi, Shreeya Khatiwada, Megha Kamath, Jake A LeSuer, Michael S Seaman, Stephen D Schmidt, John R Mascola, Dennis R Burton, Bette T Korber, Dan H Barouch
HIV-1 sequence diversity presents a major challenge for the clinical development of broadly neutralizing antibodies (bNAbs) for both therapy and prevention. Sequence variation in critical bNAb epitopes has been observed in most HIV-1-infected individuals and can lead to viral escape after bNAb monotherapy in humans. We show that viral sequence diversity can limit both the therapeutic and prophylactic efficacy of bNAbs in rhesus monkeys. We first demonstrate that monotherapy with the V3 glycan-dependent antibody 10-1074, but not PGT121, results in rapid selection of preexisting viral variants containing N332/S334 escape mutations and loss of therapeutic efficacy in simian-HIV (SHIV)-SF162P3-infected rhesus monkeys...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28931639/trispecific-broadly-neutralizing-hiv-antibodies-mediate-potent-shiv-protection-in-macaques
#3
Ling Xu, Amarendra Pegu, Ercole Rao, Nicole Doria-Rose, Jochen Beninga, Krisha McKee, Dana M Lord, Ronnie R Wei, Gejing Deng, Mark Louder, Stephen D Schmidt, Zachary Mankoff, Lan Wu, Mangaiarkarasi Asokan, Christian Beil, Christian Lange, Wulf Dirk Leuschner, Jochen Kruip, Rebecca Sendak, Young Do Kwon, Tongqing Zhou, Xuejun Chen, Robert T Bailer, Keyun Wang, Misook Choe, Lawrence J Tartaglia, Dan H Barouch, Sijy O'Dell, John-Paul Todd, Dennis R Burton, Mario Roederer, Mark Connors, Richard A Koup, Peter D Kwong, Zhi-Yong Yang, John R Mascola, Gary J Nabel
The development of an effective AIDS vaccine has been challenging due to viral genetic diversity and the difficulty in generating broadly neutralizing antibodies (bnAbs). Here, we engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: 1) the CD4 binding site, 2) the membrane proximal external region (MPER) and 3) the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to human bnAbs, and conferred complete immunity against a mixture of SHIVs in non-human primates (NHP) in contrast to single bnAbs...
September 20, 2017: Science
https://www.readbyqxmd.com/read/28929430/new-drugs-in-the-pipeline-for-the-treatment-of-hiv-a-review
#4
REVIEW
Leigh Anne Hylton Gravatt, Crystal R Leibrand, Sulay Patel, MaryPeace McRae
PURPOSE OF REVIEW: The purpose of this paper is to review therapies with new mechanisms of action for the treatment of HIV that are at least in phase 2 clinical trials. RECENT FINDINGS: There are several new mechanisms of action being represented within clinical development, including histone deacetylase (HDAC) inhibitors, gene therapies, broadly neutralizing anti-HIV antibodies, immune modulation, and drugs with new mechanisms to block HIV entry. The new therapies are being developed for both as add-on therapy to existing combination antiretroviral therapy and as agents to be used during treatment interruption...
September 19, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28928737/env-specific-antibodies-in-chronic-infection-versus-in-vaccination
#5
REVIEW
Martina Soldemo, Gunilla B Karlsson Hedestam
Antibodies are central in vaccine-mediated protection. For HIV-1, a pathogen that displays extreme antigenic variability, B cell responses against conserved determinants of the envelope glycoproteins (Env) are likely required to achieve broadly protective vaccine-induced responses. To understand antibodies in chronic infection, where broad serum neutralizing activity is observed in a subset of individuals, monoclonal antibodies mediating this activity have been isolated. Studies of their maturation pathways reveal that years of co-evolution between the virus and the adaptive immune response are required for such responses to arise...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28926408/serum-glycan-binding-igg-antibodies-in-hiv-1-infection-and-during-the-development-of-broadly-neutralizing-responses
#6
Cathrine Scheepers, Sudipa Chowdhury, W Shea Wright, Christopher T Campbell, Nigel J Garrett, Quarraisha Abdool Karim, Salim S Abdool Karim, Penny L Moore, Jeffrey C Gildersleeve, Lynn Morris
BACKGROUND: The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses. However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV infected individuals. We aimed to determine whether anti-glycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs. METHODS: IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids and Tn-peptides...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926399/natural-killer-cells-in-hiv-1-infection-and-therapy
#7
Joanna Mikulak, Ferdinando Oriolo, Elisa Zaghi, Clara Di Vito, Domenico Mavilio
: Natural killer (NK) cells are important effectors of innate immunity playing a key role in the eradication and clearance of viral infections. Over the recent years, several studies have shown that HIV-1 pathologically changes NK cell homeostasis and hampers their antiviral effector functions. Moreover, high levels of chronic HIV-1 viremia markedly impair those NK cell regulatory features that normally regulate the cross-talks between innate and adaptive immune responses. These pathogenic events take place early in the infection and are associated with a pathologic redistribution of NK cell subsets that includes the expansion of anergic CD56 NK cells with an aberrant repertoire of activating and inhibitory receptors...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28918477/in-vitro-inhibition-of-hiv-1-replication-in-autologous-cd4-t-cells-indicates-viral-containment-by-multifactorial-mechanisms
#8
Ting Tu, Jianbo Zhan, Danlei Mou, Wei Li, Bin Su, Tong Zhang, Tao Li, Ning Li, Hao Wu, Cong Jin, Huabiao Chen
HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4(+) T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures...
September 15, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28916265/glycans-function-as-anchors-for-antibodies-and-help-drive-hiv-broadly-neutralizing-antibody-development
#9
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
Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to the 3-fold axis of the envelope (Env) trimer and are among the most potent and broad Abs described. The evolution of apex bnAbs from one donor (CAP256) has been studied in detail and many Abs at different stages of maturation have been described. Using diverse engineering tools, we investigated the involvement of glycan recognition in the development of the CAP256.VRC26 Ab lineage. We found that sialic acid-bearing glycans were recognized by germline-encoded and somatically mutated residues on the Ab heavy chain...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28903577/a-2-4-amino-acid-deletion-in-the-v5-region-of-hiv-1-env-gp120-confers-viral-resistance-to-the-broadly-neutralizing-human-monoclonal-antibody-vrc01
#10
Shingo Tachibana, Maho Sasaki, Takako Tanaka, Mari Inoue, Youdiil Ophinni, Tomohiro Kotaki, Masanori Kameoka
The envelope glycoprotein (Env) gp120 of human immunodeficiency virus type 1 (HIV-1) plays a critical role in viral entry into host cells. The broadly neutralizing human monoclonal antibody VRC01, which recognizes the CD4 binding site on gp120, neutralizes more than 90% of HIV-1 isolates. However, some of the CRF01_AE viruses prevalent in Southeast Asia are resistant to VRC01-mediated neutralization. We previously reported that 3 amino acid residues at positions 185, 186, and 197 of gp120 played an important role in the VRC01 resistance of CRF01_AE Env (AE-Env) clones isolated from HIV-infected Thai individuals...
September 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28902916/targeted-n-glycan-deletion-at-the-receptor-binding-site-retains-hiv-env-nfl-trimer-integrity-and-accelerates-the-elicited-antibody-response
#11
Viktoriya Dubrovskaya, Javier Guenaga, Natalia de Val, Richard Wilson, Yu Feng, Arlette Movsesyan, Gunilla B Karlsson Hedestam, Andrew B Ward, Richard T Wyatt
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...
September 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28893278/development-of-an-anti-hiv-vaccine-eliciting-broadly-neutralizing-antibodies
#12
REVIEW
Yousuf Ahmed, Meijuan Tian, Yong Gao
The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28890135/targeted-immune-interventions-for-an-hiv-1-cure
#13
REVIEW
Matthieu Perreau, Riddhima Banga, Giuseppe Pantaleo
Combination antiretroviral therapy (cART) induces durable suppression of virus replication but is unable to eradicate HIV. Invariably, virus rebound follows treatment interruption and life-long cART is thus required. Advances have been made in our understanding of HIV latency, identification of HIV cell reservoirs, regulation of HIV-specific immune responses, as well as in the development of broad neutralizing antibodies and putative therapeutic vaccines. These have provided a scientific basis to explore alternative strategies that achieve durable suppression of viremia in the absence of cART, the so-called functional cure...
September 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28883824/natural-killer-nk-cell-education-differentially-influences-hiv-antibody-dependent-nk-cell-activation-and-antibody-dependent-cellular-cytotoxicity
#14
REVIEW
Nicole F Bernard, Zahra Kiani, Alexandra Tremblay-McLean, Sanket A Kant, Christopher E Leeks, Franck P Dupuy
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28883821/hidden-lineage-complexity-of-glycan-dependent-hiv-1-broadly-neutralizing-antibodies-uncovered-by-digital-panning-and-native-like-gp140-trimer
#15
Linling He, Xiaohe Lin, Natalia de Val, Karen L Saye-Francisco, Colin J Mann, Ryan Augst, Charles D Morris, Parisa Azadnia, Bin Zhou, Devin Sok, Gabriel Ozorowski, Andrew B Ward, Dennis R Burton, Jiang Zhu
Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878083/how-germinal-centers-evolve-broadly-neutralizing-antibodies-the-breadth-of-the-follicular-helper-t-cell-response
#16
Rob J De Boer, Alan S Perelson
Many HIV-1 infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years, and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest affinity receptors tend to acquire the most antigen from the FDC network, and present the highest density of cognate peptides to follicular helper T cells (Tfh), which provide survival signals to the B cell. BnAbs are therefore only expected to evolve when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than other lineages of more specific B cells...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28878072/high-throughput-protein-engineering-improves-the-antigenicity-and-stability-of-soluble-hiv-1-envelope-glycoprotein-sosip-trimers
#17
Jonathan T Sullivan, Chidananda Sulli, Alberto Nilo, Anila Yasmeen, Gabriel Ozorowski, Rogier W Sanders, Andrew B Ward, P J Klasse, John P Moore, Benjamin J Doranz
Soluble envelope glycoprotein (Env) trimers (SOSIP.664 gp140) are attractive HIV-1 vaccine candidates, with structures that mimic the native membrane-bound Env spike (gp160). Since engineering trimers can be limited by the difficulty of rationally predicting beneficial mutations, here we used a more comprehensive mutagenesis approach with the goal of identifying trimer variants with improved antigenic and stability properties. We created 341 cysteine pairs at predicted points of stabilization throughout gp140, 149 proline residue substitutions at every residue of the gp41 ectodomain, and 362 space-filling residue substitutions at every hydrophobic and aromatic residue in gp140...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28878010/broadly-neutralizing-antibodies-targeting-the-hiv-1-envelope-v2-apex-confer-protection-against-a-clade-c-shiv-challenge
#18
Boris Julg, Lawrence J Tartaglia, Brandon F Keele, Kshitij Wagh, Amarendra Pegu, Devin Sok, Peter Abbink, Stephen D Schmidt, Keyun Wang, Xuejun Chen, M Gordon Joyce, Ivelin S Georgiev, Misook Choe, Peter D Kwong, Nicole A Doria-Rose, Khoa Le, Mark K Louder, Robert T Bailer, Penny L Moore, Bette Korber, Michael S Seaman, Salim S Abdool Karim, Lynn Morris, Richard A Koup, John R Mascola, Dennis R Burton, Dan H Barouch
Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth against HIV-1. However, little data exist on the protective efficacy of V2-specific neutralizing antibodies. We created a novel SHIV-325c viral stock that included a clade C HIV-1 envelope and was susceptible to neutralization by both of these antibodies...
September 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28870097/glycosylation-profiling-to-evaluate-glycoprotein-immunogens-against-hiv-1
#19
Anna-Janina Behrens, Weston B Struwe, Max Crispin
Introduction Much of the efforts to develop a vaccine against the human immunodeficiency virus (HIV) have focused on the design of recombinant mimics of the viral attachment glycoprotein (Env). The leading immunogens exhibit native-like antigenic properties and are being investigated for their ability to induce broadly neutralizing antibodies (bNAbs). Understanding the relative abundance of glycans at particular glycosylation sites on these immunogens is important as most bNAbs have evolved to recognize or evade the dense coat of glycans that masks much of the protein surface...
September 5, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28858725/focus-on-the-therapeutic-efficacy-of-3bnc117-against-hiv-1-in-vitro-studies-in-vivo-studies-clinical-trials-and-challenges
#20
REVIEW
Zhi-Jun Liu, Jing Bai, Feng-Li Liu, Xiang-Yang Zhang, Jing-Zhang Wang
3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo...
August 28, 2017: International Immunopharmacology
keyword
keyword
61266
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"