Background: Susceptibility to HIV transmission by sexual intercourse has been associated with cellular anti-HIV responses. We aimed to also evaluate potential systemic humoral responses against HIV in a group of HIV-exposed seronegative individuals (HESN) in stable relationship with HIV-infected partners.
Methods: We recruited 27 serodiscordant couples. HESN were classified according to HIV exposure into very low/low and moderate/high risk. Plasma from HESN and HIV+ partners were tested for neutralizing capacity and for the recognition of cell-surface expressed and recombinant forms of HIV envelope glycoproteins (Env). Healthy individuals (healthy control, n = 11) were used as controls.
Results: Recognition of cell-surface expressed Env by both immunoglobulin (Ig)G and IgA was higher in plasma samples from HESN than in healthy controls (P = 0.0062 and P = 0.0144, respectively). IgG binding to Env was significantly increased in HESN after unmasking CD4-induced epitopes (P = 0.001), suggesting a wide range of targeted epitopes. Remarkably, ELISA assays using trimeric gp140 or monomeric gp120 failed to detect significant differences in reactivity between groups. Neutralization analysis showed residual activity in only three HESN samples (11%), whereas 70% of HIV-infected partners showed neutralizing activity. Although anti-Env humoral responses were found in 85% of HESN, their magnitude was not associated with the estimated level of exposure or the detection of HIV-specific cellular immune responses.
Conclusion: A high proportion of HESN show detectable plasma IgG or IgA recognizing different exposed and cryptic Env native epitopes unrelated to neutralizing capacity. Therefore, low but persistent HIV exposure induces new virus-specific systemic humoral responses or boosts preexisting natural antibodies.