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

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, MA

Gao, Feng

Ferrari, Guido

Shaw, George M

Haynes, Barton F

Douek, Daniel C

United States

2015-08-26T20:28:07Z

2015-08

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.

http://www.ncbi.nlm.nih.gov/pubmed/26237403

PPATHOGENS-D-15-00564

1553-7374

https://hdl.handle.net/10161/10436

eng

Public Library of Science (PLoS)

PLoS Pathog

10.1371/journal.ppat.1005042

Animals

Antibodies, Monoclonal

Antibodies, Viral

CD4-Positive T-Lymphocytes

Fluorescent Antibody Technique

HIV-1

Humans

Intestinal Mucosa

Macaca mulatta

Protein Conformation

Rectum

Reverse Transcriptase Polymerase Chain Reaction

Simian Acquired Immunodeficiency Syndrome

Simian Immunodeficiency Virus

Surface Plasmon Resonance

Viral Envelope Proteins

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

Journal article

Tomaras, Georgia D|0000-0001-8076-1931

Nicely, Nathan I|0000-0002-0025-2377

Alam, S Munir|0000-0003-0941-0703

Shen, Xiaoying|0000-0001-8076-1931|0000-0002-8387-3952

Duffy, Ryan|0000-0001-6071-1574

Montefiori, David C|0000-0003-0856-6319

Moody, MA|0000-0002-3890-5855

Gao, Feng|0000-0001-8903-0203

Ferrari, Guido|0000-0001-7747-3349

http://www.ncbi.nlm.nih.gov/pubmed/26237403

e1005042

8

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Human Vaccine Institute

Global Health Institute

Immunology

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Duke Human Vaccine Institute

Medicine, Infectious Diseases

Molecular Genetics and Microbiology

Pathology

Pediatrics

Pediatrics, Infectious Diseases

School of Medicine

Surgery

Surgery, Surgical Sciences

Surgery, Surgical Sciences Section for AIDS Research & Development

University Institutes and Centers

Published online

11