Infectious Virion Capture by HIV-1 gp120-Specific IgG from RV144 Vaccinees

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.

Progress in HIV vaccine development

“…Positive V1V2-specific complement activating Ab was also correlated with lower infection risk in RV144 vaccine recipients. 59 Therefore, though only weakly neutralizing, Ab induced by RV144 may potentially mediate protection through aggregating or immobilizing virions in mucin layers, impeding transverse through mucosal barriers, [60][61][62] via IgG Fcg receptor (FcgR) dependent ADCVI including ADCC, [55][56][57] ADCP, 56,57 Ab-mediated release of cytokines or chemokines and complement-mediated killing. [50][51][52]59,63,64 ( Fig.…”

Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development

“…Extensive analyses have been carried out seeking correlations between immune responses and reduced risk of infection (25,26,28,29,54,(74)(75)(76). The strongest correlation with reduced risk of infection was binding antibodies to the V1/ V2 region of gp120 (25,26,29,76).…”

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

“…A number of antibody‐mediated functions against HIV‐1 have been studied, including virus capture and phagocytosis,9, 10 antibody‐dependent cell‐mediated virus inhibition,11, 12 antibody‐dependent cell‐mediated cytotoxicity (ADCC),13, 14 chemokine secretion of monocytes stimulated by antibodies,15 and virus neutralization 16, 17, 18. Neutralization has been shown to exert immune pressure on HIV‐1,19, 20 while the role of other antibody‐mediated functions in exerting immune pressure is unclear, primarily because antibodies that mediate ADCC and other activities often also neutralize 21.…”