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EBioMedicine. 2014 Nov 1;1(1):37-45.

Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses.

Author information

1
New York Veterans Affairs Harbor Healthcare System, 423 East 23 Street, New York, NY 10010, USA ; New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
2
Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA.
3
Department of Retrovirology, Walter Reed Army Institute of Research, Building 503, Silver Spring, MD 20910, USA.
4
New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
5
Department of Microbiology, University of Washington, 358B Rosen Building, Campus box 358070, Seattle, WA 98195.
6
Thai Red Cross AIDS Research Center 104, Tower 2, Rajdumari Rd. Pathumwan, Bangkok, Thailand, 10330.
7
Armed Forces Research Institute of Medical Science (AFRIMS) Department of Retrovirology Humoral Immunology and Assessment Laboratory, 315/6 Rajvithi Rd. Bangkok, 10400, Thailand.
8
Department of Disease Control, Ministry of Public Health, Nonthaburi, 11000, Thailand.
9
Department of Clinical Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand.
10
U.S. Army Military HIV Research Program, 6720A Rockledge Dr., Suite 400, Bethesda MD, 20817.

Abstract

To evaluate the role of V3-specific IgG antibodies (Abs) in the RV144 clinical HIV vaccine trial, which reduced HIV-1 infection by 31.2%, the anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE breakthrough viruses from 43 vaccine- and 66 placebo-recipients demonstrated an estimated vaccine efficacy of 85% against viruses with amino acids mismatching the vaccine at V3 site 317 (p=0.004) and 52% against viruses matching the vaccine at V3 site 307 (p=0.004). This analysis was supported by data showing vaccinees' plasma Abs were less reactive with I307 replaced with residues found more often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F317 were less infectious, possibly due to the contribution of F317 to optimal formation of the V3 hydrophobic core. These data suggest that RV144-induced V3-specific Abs imposed immune pressure on infecting viruses and inform efforts to design an HIV vaccine.

KEYWORDS:

HIV; antibody; clinical trial; vaccine

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