title: Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses.
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 I307replaced with residues found more often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F317were less infectious, possibly due to the contribution of F317to 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.
authors.affiliation: 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.
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.affiliation: Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.affiliation: Department of Retrovirology, Walter Reed Army Institute of Research, Building 503, Silver Spring, MD 20910, USA.
authors.forename: Morgane
authors.initials: M
authors.lastname: Rolland
authors.affiliation: New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Xiang-Peng
authors.initials: XP
authors.lastname: Kong
authors.affiliation: Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: deCamp
authors.affiliation: Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.affiliation: New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Constance
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Retrovirology, Walter Reed Army Institute of Research, Building 503, Silver Spring, MD 20910, USA.
authors.forename: Sodsai
authors.initials: S
authors.lastname: Tovanabutra
authors.affiliation: New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sharpe-Cohen
authors.affiliation: Department of Microbiology, University of Washington, 358B Rosen Building, Campus box 358070, Seattle, WA 98195.
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.affiliation: Thai Red Cross AIDS Research Center 104, Tower 2, Rajdumari Rd. Pathumwan, Bangkok, Thailand, 10330.
authors.forename: Mark S
authors.initials: MS
authors.lastname: deSouza
authors.affiliation: Armed Forces Research Institute of Medical Science (AFRIMS) Department of Retrovirology Humoral Immunology and Assessment Laboratory, 315/6 Rajvithi Rd. Bangkok, 10400, Thailand.
authors.forename: Nicos
authors.initials: N
authors.lastname: Karasavvas
authors.affiliation: Armed Forces Research Institute of Medical Science (AFRIMS) Department of Retrovirology Humoral Immunology and Assessment Laboratory, 315/6 Rajvithi Rd. Bangkok, 10400, Thailand.
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: Department of Disease Control, Ministry of Public Health, Nonthaburi, 11000, Thailand.
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.affiliation: Department of Clinical Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttihum
authors.affiliation: Department of Clinical Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Armed Forces Research Institute of Medical Science (AFRIMS) Department of Retrovirology Humoral Immunology and Assessment Laboratory, 315/6 Rajvithi Rd. Bangkok, 10400, Thailand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.affiliation: U.S. Army Military HIV Research Program, 6720A Rockledge Dr., Suite 400, Bethesda MD, 20817.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: U.S. Army Military HIV Research Program, 6720A Rockledge Dr., Suite 400, Bethesda MD, 20817.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: U.S. Army Military HIV Research Program, 6720A Rockledge Dr., Suite 400, Bethesda MD, 20817.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Gilbert
keywords: HIV; antibody; clinical trial; vaccine