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https://www.readbyqxmd.com/read/29669274/superinfection-drives-hiv-neutralizing-antibody-responses-from-several-b-cell-lineages-that-contribute-to-a-polyclonal-repertoire
#1
Katherine L Williams, Bingjie Wang, Dana Arenz, James A Williams, Adam S Dingens, Valerie Cortez, Cassandra A Simonich, Stephanie Rainwater, Dara A Lehman, Kelly K Lee, Julie Overbaugh
Eliciting broad and potent HIV-specific neutralizing antibody responses represents the holy grail of HIV vaccine efforts. Data from singly infected individuals with broad and potent plasma neutralizing activity targeting one epitope have guided our understanding of how these responses develop. However, far less is known about responses developed by superinfected individuals who acquire two distinct HIV strains. Here, we isolated HIV-specific mAbs from a superinfected individual with a broad plasma response...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29643249/neutralizing-antibody-responses-following-long-term-vaccination-with-hiv-1-env-gp140-in-guinea-pigs
#2
Christine A Bricault, James M Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L Shields, Bronwyn M Gunn, George H Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P Nkolola, Galit Alter, Bing Chen, Kathryn E Stephenson, Nicole Doria-Rose, John R Mascola, Michael S Seaman, Dan H Barouch
A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here we report the immunogenicity of longitudinal prime/boost vaccination regimens over a period of 200 weeks in guinea pigs with a panel of HIV-1 envelope (Env) gp140 protein immunogens. We assessed vaccine regimens that included a monovalent clade C gp140 regimen (C97), a tetravalent regimen consisting of four clade C gp140s (4C), and a tetravalent regimen consisting of a clade A, B, C, and mosaic gp140 (ABCM)...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29579256/characterization-of-the-neutralizing-antibody-response-in-a-case-of-genetically-linked-hiv-superinfection
#3
Deogratius Ssemwanga, Nicole A Doria-Rose, Andrew D Redd, Andrea R Shiakolas, Andrew F Longosz, Rebecca N Nsubuga, Billy N Mayanja, Gershim Asiki, Janet Seeley, Anatoli Kamali, Amy Ransier, Samuel Darko, Michael P Walker, Daniel Bruno, Craig Martens, Daniel Douek, Stephen F Porcella, Thomas C Quinn, John R Mascola, Pontiano Kaleebu
This report describes the identification of a genetically confirmed linked heterosexual human immunodeficiency virus (HIV) superinfection (HIV-SI) in a woman with chronic HIV infection who acquired a second strain of the virus from her husband. Serum neutralizing antibody (NAb) responses against their homologous and heterologous viruses, including the superinfecting strain, in the woman and her husband were examined before and after onset of HIV-SI. The woman displayed a moderately potent and broad anti-HIV NAb response prior to superinfection but did not possess NAb activity against the superinfecting strain...
March 22, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29474444/epitopes-for-neutralizing-antibodies-induced-by-hiv-1-envelope-glycoprotein-bg505-sosip-trimers-in-rabbits-and-macaques
#4
P J Klasse, Thomas J Ketas, Christopher A Cottrell, Gabriel Ozorowski, Gargi Debnath, Diawoye Camara, Erik Francomano, Pavel Pugach, Rajesh P Ringe, Celia C LaBranche, Marit J van Gils, Christine A Bricault, Dan H Barouch, Shane Crotty, Guido Silvestri, Sudhir Kasturi, Bali Pulendran, Ian A Wilson, David C Montefiori, Rogier W Sanders, Andrew B Ward, John P Moore
The native-like, soluble SOSIP.664 trimer based on the BG505 clade A env gene of HIV-1 is immunogenic in various animal species, of which the most studied are rabbits and rhesus macaques. The trimer induces autologous neutralizing antibodies (NAbs) consistently but at a wide range of titers and with incompletely determined specificities. A precise delineation of immunogenic neutralization epitopes on native-like trimers could help strategies to extend the NAb response to heterologous HIV-1 strains. One autologous NAb epitope on the BG505 Env trimer is known to involve residues lining a hole in the glycan shield that is blocked by adding a glycan at either residue 241 or 289...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29367243/immunogenicity-in-rabbits-of-hiv-1-sosip-trimers-from-clades-a-b-and-c-given-individually-sequentially-or-in-combination
#5
Alba Torrents de la Peña, Steven W de Taeye, Kwinten Sliepen, Celia C LaBranche, Judith A Burger, Edith E Schermer, David C Montefiori, John P Moore, Per Johan Klasse, Rogier W Sanders
Recombinant soluble HIV-1 envelope glycoprotein (Env) SOSIP trimers are a design platform for inducing broadly neutralizing antibodies (bNAbs) by vaccination. To date, these and alternative designs of native-like trimers, given singly or in pairs, have not induced bNAbs in test animals such as rabbits or macaques. Here, we have evaluated whether trivalent and tetravalent combinations of SOSIP trimers from clades A, B, and C, delivered simultaneously or sequentially, induce better neutralizing antibody responses in rabbits than when given alone...
April 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343576/increased-epitope-complexity-correlated-with-antibody-affinity-maturation-and-a-novel-binding-mode-revealed-by-structures-of-rabbit-antibodies-against-the-third-variable-loop-v3-of-hiv-1-gp120
#6
Ruimin Pan, Yali Qin, Marisa Banasik, William Lees, Adrian J Shepherd, Michael W Cho, Xiang-Peng Kong
The V3 loop of HIV-1 gp120 is an immunodominant region targeted by neutralizing antibodies (nAbs). Despite limited breadth, better characterization of the structural details of the interactions between these nAbs and their target epitopes would enhance our understanding of the mechanism of neutralization and facilitate designing better immunogens to induce nAbs with greater breadth. Recently, we isolated two anti-V3 neutralizing monoclonal antibodies (mAbs), 10A3 and 10A37, from a rabbit immunized with gp120 of the M group consensus sequence...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29315059/multi-envelope-hiv-1-vaccine-development-two-targeted-immune-pathways-one-desired-protective-outcome
#7
Julia L Hurwitz, Mattia Bonsignori
In 2016, there were more than 30 million individuals living with HIV-1, ∼1.8 million new HIV-1 infections, and ∼1 million HIV-1-related deaths according to UNAIDS ( unaids.org ). Hence, a preventive HIV-1 vaccine remains a global priority. The variant envelopes of HIV-1 present a significant obstacle to vaccine development and the vaccine field has realized that immunization with a single HIV-1 envelope protein will not be sufficient to generate broadly neutralizing antibodies. Here we describe two nonmutually exclusive, targeted pathways with which a multi-envelope HIV-1 vaccine may generate protective immune responses against variant HIV-1...
January 9, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29281818/vaccine-induction-of-heterologous-tier-2-hiv-1-neutralizing-antibodies-in-animal-models
#8
Kevin O Saunders, Laurent K Verkoczy, Chuancang Jiang, Jinsong Zhang, Robert Parks, Haiyan Chen, Max Housman, Hilary Bouton-Verville, Xiaoying Shen, Ashley M Trama, Richard Scearce, Laura Sutherland, Sampa Santra, Amanda Newman, Amanda Eaton, Kai Xu, Ivelin S Georgiev, M Gordon Joyce, Georgia D Tomaras, Mattia Bonsignori, Steven G Reed, Andres Salazar, John R Mascola, M Anthony Moody, Derek W Cain, Mireille Centlivre, Sandra Zurawski, Gerard Zurawski, Harold P Erickson, Peter D Kwong, S Munir Alam, Yves Levy, David C Montefiori, Barton F Haynes
The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VH DJH ) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH  chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s...
December 26, 2017: Cell Reports
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
#9
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 to the HIV-1 envelope glycoprotein (Env) 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 broadly neutralizing antibody epitopes but limit the presentation of immunodominant non-NAb epitopes that might induce off-target and potentially interfering responses...
February 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29209323/non-neutralizing-antibodies-directed-against-hiv-and-their-functions
#10
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/29162799/structure-based-design-of-native-like-hiv-1-envelope-trimers-to-silence-non-neutralizing-epitopes-and-eliminate-cd4-binding
#11
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/29150603/bacterially-derived-synthetic-mimetics-of-mammalian-oligomannose-prime-antibody-responses-that-neutralize-hiv-infectivity
#12
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
#13
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
https://www.readbyqxmd.com/read/29066544/maternal-but-not-infant-anti-hiv-1-neutralizing-antibody-response-associates-with-enhanced-transmission-and-infant-morbidity
#14
Melissa Ghulam-Smith, Alex Olson, Laura F White, Charles S Chasela, Sascha R Ellington, Athena P Kourtis, Denise J Jamieson, Gerald Tegha, Charles M van der Horst, Manish Sagar
A significant number of infants acquire HIV-1 through their infected mother's breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting results about the ability of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant outcomes. This study compared plasma neutralizing activity in exposed infants and the infected mothers ( n = 63) against heterologous HIV-1 variants and the quasispecies present in the mother...
October 24, 2017: MBio
https://www.readbyqxmd.com/read/29020058/hiv-transmitted-founder-vaccines-elicit-autologous-tier-2-neutralizing-antibodies-for-the-cd4-binding-site
#15
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/28928750/the-role-of-maternal-hiv-envelope-specific-antibodies-and-mother-to-child-transmission-risk
#16
REVIEW
Ayooluwa O Douglas, David R Martinez, Sallie R Permar
Despite the wide availability of antiretroviral therapy (ART) prophylaxis during pregnancy, >150,000 infants become infected through mother-to-child transmission (MTCT) of HIV worldwide. It is likely that additional intervention strategies, such as a maternal HIV vaccine, will be required to eliminate pediatric HIV infections. A deeper understanding of the fine specificity and function of maternal HIV envelope (Env)-specific responses that provide partial protection against MTCT will be critical to inform the design of immunologic strategies to curb the pediatric HIV epidemic...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28918477/in-vitro-inhibition-of-hiv-1-replication-in-autologous-cd4-t-cells-indicates-viral-containment-by-multifactorial-mechanisms
#17
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...
December 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28841647/probing-the-compartmentalization-of-hiv-1-in-the-central-nervous-system-through-its-neutralization-properties
#18
Karl Stefic, Antoine Chaillon, Mélanie Bouvin-Pley, Alain Moreau, Martine Braibant, Frédéric Bastides, Guillaume Gras, Louis Bernard, Francis Barin
Compartmentalization of HIV-1 has been observed in the cerebrospinal fluid (CSF) of patients at different clinical stages. Considering the low permeability of the blood-brain barrier, we wondered if a reduced selective pressure by neutralizing antibodies (NAb) in the central nervous system (CNS) could favor the evolution of NAb-sensitive viruses in this compartment. Single genome amplification (SGA) was used to sequence full-length HIV-1 envelope variants (453 sequences) from paired CSF and blood plasma samples in 9 subjects infected by HIV variants of various clades and suffering from diverse neurologic disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28835491/hiv-1-cross-reactive-primary-virus-neutralizing-antibody-response-elicited-by-immunization-in-nonhuman-primates
#19
Yimeng Wang, Sijy O'Dell, Hannah L Turner, Chi-I Chiang, Lin Lei, Javier Guenaga, Richard Wilson, Paola Martinez-Murillo, Nicole Doria-Rose, Andrew B Ward, John R Mascola, Richard T Wyatt, Gunilla B Karlsson Hedestam, Yuxing Li
Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates elicit predominantly tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28834745/improving-the-immunogenicity-of-native-like-hiv-1-envelope-trimers-by-hyperstabilization
#20
Alba Torrents de la Peña, Jean-Philippe Julien, Steven W de Taeye, Fernando Garces, Miklos Guttman, Gabriel Ozorowski, Laura K Pritchard, Anna-Janina Behrens, Eden P Go, Judith A Burger, Edith E Schermer, Kwinten Sliepen, Thomas J Ketas, Pavel Pugach, Anila Yasmeen, Christopher A Cottrell, Jonathan L Torres, Charlotte D Vavourakis, Marit J van Gils, Celia LaBranche, David C Montefiori, Heather Desaire, Max Crispin, Per Johan Klasse, Kelly K Lee, John P Moore, Andrew B Ward, Ian A Wilson, Rogier W Sanders
The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation...
August 22, 2017: Cell Reports
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