There is an urgent need for a HIV-1 vaccine. A better understanding of the immune parameters present during natural HIV-1 exposure might inform vaccine design. Semen - an overlooked factor in models of HIV-1 infection - not only acts as a vehicle for HIV-1 transmission, but might also initiate or attenuate anti-viral immune responses at the mucosal site of exposure. We have previously demonstrated seminal plasma (SP) to potently inhibit anti-viral NK cell and cytotoxic T-lymphocyte responses in vitro. In addition to inhibitory factors, SP from HIV-1-infected donors contain anti-HIV-1 antibodies. We now present data characterizing anti-HIV-1 antibodies within semen from paired samples obtained prior to and following initiation of antiretroviral therapy (ART).
Matched serum and SP samples were collected from 11 HIV-1-infected donors at pre- and during-ART time points. These samples were assessed by end-point titer ELISAs for anti-gp120 IgG. Both serum and SP samples collected after greater than six months of ART exhibited a non-significant decrease in levels of anti-gp120 antibodies, compared to pre-ART samples [median 2.0 log10 vs 2.5 log10, p=0.218, n=8]. Furthermore, we observed no significant differences in NK cell IFNγ production following stimulation with gp120-coated T cells in the presence of purified IgG from pre-ART or during-ART SP samples [2.85% (15.04–0.17) vs 4.57% (14.33–0.23), p=0.465, n=11]. Lastly, we noted that antibodies capable of mediating antibody-dependent cellular cytoxicity within serum and SP targeted similar gp120 epitopes. Pre-incubation of gp120-coated T cells with a FAb of an anti-HIV-1 antibody directed to a CD4-induced epitope within gp120 inhibited anti-HIV-1 antibody-dependent NK cell activation by sera and SP-derived IgG [median 70.0% inhibition, p=0.0039, n=9].
Our findings highlight the presence of functional anti-HIV-1- antibodies within SP that target similar epitopes on gp120 as sera antibodies. Future research should investigate the role these anti-HIV-1 seminal antibodies play during mucosal HIV-1 transmission.