Journal
JOURNAL OF VIROLOGY
Volume 87, Issue 14, Pages 7828-7836Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02737-12
Keywords
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Funding
- Bill and Melinda Gates Foundation [1032144, 1033098]
- National Institutes of Health (NIH/NIAID/DAIDS)
- Center for HIV/AIDS Vaccine Immunology [U01 AI067854]
- HIV-1 Vaccine Trials Network [5U01 AI46725-05]
- Duke University Center for AIDS Research (CFAR) [P30 AI 64518]
- UAB CFAR [P30 AI 27767]
- U.S. Army Medical Research and Material Command through Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [Y1-AI-2642-12, W81XWH-07-2-0067]
- National Institutes of Allergy and Infectious Diseases (NIAID) through Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [Y1-AI-2642-12, W81XWH-07-2-0067]
- U.S. Army Medical Research and Material Command through U.S. Department of Defense (DOD) [Y1-AI-2642-12, W81XWH-07-2-0067]
- National Institutes of Allergy and Infectious Diseases (NIAID) through U.S. Department of Defense (DOD) [Y1-AI-2642-12, W81XWH-07-2-0067]
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The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent assay limitations, as well as the need to keep the correlates analysis focused on a limited number of endpoints to achieve statistical power. In an RV144 pilot study, we determined that RV144 vaccination elicited antibodies that could bind infectious virions (including the vaccine strains HIV-1 CM244 and HIV-1 MN and an HIV-1 strain expressing transmitted/founder Env, B.WITO.c). Among vaccinees with the highest IgG binding antibody profile, the majority (78%) captured the infectious vaccine strain virus (CM244), while a smaller proportion of vaccinees (26%) captured HIV-1 transmitted/founder Env virus. We demonstrated that vaccine-elicited HIV-1 gp120 antibodies of multiple specificities (V3, V2, conformational C1, and gp120 conformational) mediated capture of infectious virions. Although capture of infectious HIV-1 correlated with other humoral immune responses, the extent of variation between these humoral responses and virion capture indicates that virion capture antibodies occupy unique immunological space.
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