P40.06
Background: The RV144 vaccine trial yielded results of 31.2% efficacy in protection from HIV-1 infection, despite a lack of broadly neutralising antibodies (BnAb). Subsequent analysis has demonstrated a correlate of protection was high ADCC (antibody-derived cellular cytotoxicity) IgG and low levels of IgA antibodies to the V1V2 region of env. Here, we investigate the ability of a range of neutralising (nAb) and non-neutralising (nnAb) antibodies to prevent or lower HIV-1 infection in cellular and tissue explant models.
Methods: A range of monoclonal antibodies with discrete epitope specificity and structure isolated by the CHAVI consortium from vaccinated and infected subjects have been screened in cellular and tissue based models designed to mimic the initial events in transmission.
Results: A range of nnAbs and nAbs were screened for activity against HIV-1BaL infection of macrophages, dendritic cells, dendritic trans/cis infection of T cells, and mucosal explants. 21/25 nnAbs displayed no antiviral activity in these models. Four nnAbs had inhibitory activity against macrophage infection, however none had any inhibitory activity against infection of mucosal tissue explants (rectal, penile, cervical). Only the nAb CH31 displayed inhibitory activity across all models.
Conclusions: To date only nAb have been able to prevent infection across all models tested. These data suggest that nnAbs may be insufficient to prevent the initial infection of target cells in mucosal tissue. Nevertheless, these conclusions come with caveats. First, experiments were performed with HIV-1BaL, there may be differential activity against other strains. Second, polyclonal nnAbs may show increased function. Third, the tissue explant models represent a static system with no influx of effector cells. Although such explants contain numerous cells capable of performing effector functions, it cannot be excluded that initial infection in vivo could result in recruitment of additional effector cells able to control or eliminate infection.
