Anti-Gag antibodies gag HIV infection and slow disease progression

OBJECTIVE: Post-infection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. DESIGN: Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naïve participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential. METHOD: Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated NK cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) respectively. RESULTS: p24 IgG1 was the only subclass associated with viral control (p=0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in subjects with elevated Gag-specific T cell responses, these levels remained an independent predictor of low viral loads (p=0.04) and high CD4 counts (p=0.004) after adjusting for Gag-specific T cell responses and for protective HLA class I alleles. CONCLUSION: p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.