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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.

dc.contributor.author Alam, S Munir
dc.contributor.author Blair, Lily M
dc.contributor.author Chao, A
dc.contributor.author Cocklin, SL
dc.contributor.author Dennison, SM
dc.contributor.author Duffy, R
dc.contributor.author Evans, A
dc.contributor.author Ferrari, Guido
dc.contributor.author Forthal, DN
dc.contributor.author Gao, Feng
dc.contributor.author Giorgi, EE
dc.contributor.author Haynes, Barton Ford
dc.contributor.author Kaewkungwal, J
dc.contributor.author Kim, JH
dc.contributor.author Klein, Katja
dc.contributor.author Korber, Bette T
dc.contributor.author Kumar, A
dc.contributor.author Landucci, G
dc.contributor.author Letvin, NL
dc.contributor.author Li, H
dc.contributor.author Liao, Hua-Xin
dc.contributor.author Liu, P
dc.contributor.author Michael, NL
dc.contributor.author Montefiori, David Charles
dc.contributor.author Moody, M Anthony
dc.contributor.author Moog, C
dc.contributor.author Nicely, NI
dc.contributor.author Nitayaphan, Sorachai
dc.contributor.author Pemble IV, Charles W
dc.contributor.author Pitisuttithum, P
dc.contributor.author Pollara, Justin Joseph
dc.contributor.author Rerks-Ngarm, S
dc.contributor.author Robb, ML
dc.contributor.author Robinson, J
dc.contributor.author Santra, Sampa
dc.contributor.author Schmitz, Joern E
dc.contributor.author Schutte, RJ
dc.contributor.author Shattock, RJ
dc.contributor.author Shaw, GM
dc.contributor.author Shen, X
dc.contributor.author Soderberg, Kelly
dc.contributor.author Tomaras, Georgia Doris
dc.contributor.author Vidnovic, K
dc.contributor.author Warrier, R
dc.contributor.author Xia, Shi-Mao
dc.contributor.author Zhang, R
dc.coverage.spatial United States
dc.date.accessioned 2015-08-26T20:28:07Z
dc.date.issued 2015-08
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/26237403
dc.identifier PPATHOGENS-D-15-00564
dc.identifier.uri https://hdl.handle.net/10161/10436
dc.description.abstract 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.
dc.language eng
dc.relation.ispartof PLoS Pathog
dc.relation.isversionof 10.1371/journal.ppat.1005042
dc.subject Animals
dc.subject Antibodies, Monoclonal
dc.subject Antibodies, Viral
dc.subject CD4-Positive T-Lymphocytes
dc.subject Fluorescent Antibody Technique
dc.subject HIV-1
dc.subject Humans
dc.subject Intestinal Mucosa
dc.subject Macaca mulatta
dc.subject Protein Conformation
dc.subject Rectum
dc.subject Reverse Transcriptase Polymerase Chain Reaction
dc.subject Simian Acquired Immunodeficiency Syndrome
dc.subject Simian Immunodeficiency Virus
dc.subject Surface Plasmon Resonance
dc.subject Viral Envelope Proteins
dc.title Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/26237403
pubs.begin-page e1005042
pubs.issue 8
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Global Health Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pathology
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Infectious Diseases
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group Surgery, Surgical Sciences Section for AIDS Research & Development
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 11
dc.identifier.eissn 1553-7374


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