Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses
Susan Zolla-Pazner,
Paul T. Edlefsen,
Morgane Rolland,
Xiang-Peng Kong,
Allan deCamp,
Raphael Gottardo,
Constance Williams,
Sodsai Tovanabutra,
Sandra Sharpe-Cohen,
James I. Mullins,
Mark S. deSouza,
Nicos Karasavvas,
Sorachai Nitayaphan,
Supachai Rerks-Ngarm,
Punnee Pitisuttihum,
Jaranit Kaewkungwal,
Robert J. O'Connell,
Merlin L. Robb,
Nelson L. Michael,
Jerome H. Kim,
Peter Gilbert
Affiliations
Susan Zolla-Pazner
New York Veterans Affairs Harbor Healthcare System, 423 East 23rd Street, New York, NY 10010, USA
Paul T. Edlefsen
Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA
Morgane Rolland
Department of Retrovirology, Walter Reed Army Institute of Research, Building 503, Silver Spring, MD 20910, USA
Xiang-Peng Kong
New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Allan deCamp
Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA
Raphael Gottardo
Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA
Constance Williams
New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Sodsai Tovanabutra
Department of Retrovirology, Walter Reed Army Institute of Research, Building 503, Silver Spring, MD 20910, USA
Sandra Sharpe-Cohen
New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
James I. Mullins
Department of Microbiology, University of Washington, 358B Rosen Building, Campus Box 358070, Seattle, WA 98195, USA
Mark S. deSouza
Thai Red Cross AIDS Research Center 104, Tower 2, Rajdamri Rd., Pathumwan, Bangkok 10330, Thailand
Nicos Karasavvas
Armed Forces Research Institute of Medical Science (AFRIMS) Department of Retrovirology, Humoral Immunology and Assessment Laboratory, 315/6 Rajvithi Rd., Bangkok 10400, Thailand
Sorachai Nitayaphan
Armed Forces Research Institute of Medical Science (AFRIMS) Department of Retrovirology, Humoral Immunology and Assessment Laboratory, 315/6 Rajvithi Rd., Bangkok 10400, Thailand
Supachai Rerks-Ngarm
Department of Disease Control, Ministry of Public Health, Nonthaburi 11000, Thailand
Punnee Pitisuttihum
Department of Clinical Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand
Jaranit Kaewkungwal
Department of Clinical Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand
Robert J. O'Connell
Armed Forces Research Institute of Medical Science (AFRIMS) Department of Retrovirology, Humoral Immunology and Assessment Laboratory, 315/6 Rajvithi Rd., Bangkok 10400, Thailand
Merlin L. Robb
U.S. Army Military HIV Research Program, 6720A Rockledge Dr., Suite 400, Bethesda, MD 20817, USA
Nelson L. Michael
U.S. Army Military HIV Research Program, 6720A Rockledge Dr., Suite 400, Bethesda, MD 20817, USA
Jerome H. Kim
U.S. Army Military HIV Research Program, 6720A Rockledge Dr., Suite 400, Bethesda, MD 20817, USA
Peter Gilbert
Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA
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 that vaccinees' plasma Abs were less reactive with I307 when 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.
