Relative reactivity of HIV-1 polyclonal plasma antibodies directed to V3 and MPER regions suggests immunodominance of V3 over MPER and dependence of high anti-V3 antibody titers on virus persistence

Antibodies to two crucial regions, the third variable loop (V3) of gp120 and the membrane-proximal external region (MPER) of gp41 are important for HIV-1 neutralization. We here evaluated the relative binding of polyclonal plasma antibodies from 99 HIV-1-infected individuals from India to the consensus–C V3 and MPER peptides and observed immunodominance of V3 over MPER ( p < 0.0001). We further examined the V3- and MPER-specific antibody correlates with clinical parameters. Our results revealed that anti-V3 antibody titers are significantly lower in patients on ART compared to drug-naive individuals ( p < 0.0001), most likely due to a decrease in plasma viral load, irrespective of their CD4 counts and total IgG. No such association was observed for MPER, with a similar trend in four follow-up patients. These findings strongly suggest that high titers of V3-specific antibodies are dependent on persistence of virus in circulation, while antibodies to MPER are probably not.