Understanding immune control of HIV infection in controllers should facilitate the development of therapeutic HIV vaccines. While CD8+ T cell responses to Gag proteins restricted by ‘protective’ HLA alleles exert a dominant effect, other immune responses also contribute to immune control. We have shown that IgG antibodies to HIV Gag proteins that have undergone isotype diversification, to include IgG2 as well as IgG1, may contribute to immune control and, furthermore, could be enhanced by vaccination (French MA et al. AIDS 2010 and 2013). We have investigated this further by optimising methods for demonstrating diversification of IgG antibodies to HIV p24.
Plasma samples from HIV controllers (n=14) and non-controllers (n=20) were examined for antibodies by ELISA using two forms of recombinant HIV p24 (cloned in E. coli or baculovirus) and native p24 protein as antigens. Assay conditions were optimised to minimise detection of low affinity antibodies detected in serum from non-HIV donors. Calibration was undertaken using sera containing high amounts of antibody and results expressed in arbitrary units. results: There were strong correlations between plasma levels of IgG1 and IgG2 antibodies to HIV p24 using E. coli-p24, baculovirus-p24 and native-p24 as antigens in HIV controllers (p<0.0001, 0.02, <0.0001, respectively) but not in non-controllers. Plasma levels of IgG1 antibodies to HIV p24 were higher in controllers than non-controllers using all 3 antigens (p=0.05, 0.04, 0.03, respectively) and the differences were even more pronounced for IgG2 antibodies to HIV p24 (p=0.005, 0.02, 0.003, respectively). Analyses in a single controller without ‘protective’ HLA-B alleles who progressed from an elite to a viraemic controller over 5 years demonstrated an inverse correlation between plasma HIV RNA levels and the ratio of IgG2/IgG1 antibody to HIV p24 (p=0.016).
Conclusion: Isotype diversification of IgG antibodies to HIV p24 is associated with natural control of HIV infection.
