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Infectious Virion Capture by HIV-1 gp120-Specific IgG from RV144 Vaccinees
Authors:Pinghuang Liu  Nicole L Yates  Xiaoying Shen  Mattia Bonsignori  M Anthony Moody  Hua-Xin Liao  Youyi Fong  S Munir Alam  R Glenn Overman  Thomas Denny  Guido Ferrari  Christina Ochsenbauer  John C Kappes  Victoria R Polonis  Punnee Pitisuttithum  Jaranit Kaewkungwal  Sorachai Nitayaphan  Supachai Rerks-Ngarm  David C Montefiori  Peter Gilbert  Nelson L Michael  Jerome H Kim  Barton F Haynes  Georgia D Tomaras
Abstract: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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