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Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

PLoS pathogens, 2015-08, Vol.11 (8), p.e1005042-e1005042 [Peer Reviewed Journal]

COPYRIGHT 2015 Public Library of Science ;COPYRIGHT 2015 Public Library of Science ;2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Santra S, Tomaras GD, Warrier R, Nicely NI, Liao H-X, Pollara J, et al. (2015) Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog 11(8): e1005042. doi:10.1371/journal.ppat.1005042 ;ISSN: 1553-7374 ;ISSN: 1553-7366 ;EISSN: 1553-7374 ;DOI: 10.1371/journal.ppat.1005042 ;PMID: 26237403

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Title:
Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques
Author: Santra, Sampa ; Tomaras, Georgia D ; Warrier, Ranjit ; Nicely, Nathan I ; Liao, Hua-Xin ; Pollara, Justin ; Liu, Pinghuang ; Alam, S Munir ; Zhang, Ruijun ; Cocklin, Sarah L ; Shen, Xiaoying ; Duffy, Ryan ; Xia, Shi-Mao ; Schutte, Robert J ; Pemble Iv, Charles W ; Dennison, S Moses ; Li, Hui ; Chao, Andrew ; Vidnovic, Kora ; Evans, Abbey ; Klein, Katja ; Kumar, Amit ; Robinson, James ; Landucci, Gary ; Forthal, Donald N ; Montefiori, David C ; Kaewkungwal, Jaranit ; Nitayaphan, Sorachai ; Pitisuttithum, Punnee ; Rerks-Ngarm, Supachai ; Robb, Merlin L ; Michael, Nelson L ; Kim, Jerome H ; Soderberg, Kelly A ; Giorgi, Elena E ; Blair, Lily ; Korber, Bette T ; Moog, Christiane ; Shattock, Robin J ; Letvin, Norman L ; Schmitz, Joern E ; Moody, M A ; Gao, Feng ; Ferrari, Guido ; Shaw, George M ; Haynes, Barton F
Douek, Daniel C.
Subjects: Acquired immune deficiency syndrome ; AIDS ; Animals ; antibodies ; Antibodies, Monoclonal - immunology ; Antibodies, Viral - immunology ; BASIC BIOLOGICAL SCIENCES ; CD4-Positive T-Lymphocytes - immunology ; Crystal structure ; Crystallography ; enzyme-linked immunoassays ; Fluorescent Antibody Technique ; Health aspects ; HIV ; HIV (Viruses) ; HIV-1 ; HIV-1 - immunology ; Host-virus relationships ; Human immunodeficiency virus ; Humans ; Immunoglobulins ; Immunology ; Infections ; Intestinal Mucosa - virology ; Macaca mulatta ; macaque ; macrophages ; Monoclonal antibodies ; Mutation ; Observations ; Protein Conformation ; Rectum ; Reverse Transcriptase Polymerase Chain Reaction ; Rhesus monkey ; rhesus monkeys ; Simian Acquired Immunodeficiency Syndrome - prevention & control ; Simian Immunodeficiency Virus - immunology ; Surface Plasmon Resonance ; T cells ; Vaccines ; Viral Envelope Proteins - chemistry ; Viral Envelope Proteins - immunology ; Viral infections ; virions ; Viruses
Is Part Of: PLoS pathogens, 2015-08, Vol.11 (8), p.e1005042-e1005042
Description: HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1553-7374
ISSN: 1553-7366
EISSN: 1553-7374
DOI: 10.1371/journal.ppat.1005042
PMID: 26237403
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
Public Library of Science (PLoS)
ProQuest Central
DOAJ Directory of Open Access Journals

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Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

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