Do helminth infections confound human clinical Phase 3 HIV vaccine efficacy? A first look 3186

Abstract Description We hypothesize clinical HIV vaccine efficacy testing is confounded by infections with neglected tropical diseases (NTD), such as chronic infection with the helminth parasite Schistosoma mansoni. Effective HIV vaccines likely require Tc1/Th1 immunity, which is impaired during chronic schistosomiasis. In fact, the only HIV vaccine showing even modest efficacy (RV144) was tested in Thailand, which is not endemic for schistosomiasis, whereas similar strategies (HVTN 097, 100, 702, 705) tested in South Africa, where schistosomiasis is highly prevalent, failed to show efficacy. Here, we are evaluating HVTN 705 participants for helminth infection through indirect ELISA of sera against S. mansoni antigens. This assay will cross-react with other helminths; this non-specific test will determine if a participant has at least one worm infection without needing to screen for multiple species separately. We will stratify participants based on ELISA results and evaluate correlations with immunogenicity and efficacy data. We expect helminth-infected groups will have lower Tc1/Th1 immunogenicity, leading to lower HIV vaccine efficacy. We have spent too long testing vaccines in areas with high incidence of HIV infection, which are also co-endemic for helminths, without consideration for the confounding aspects of these NTDs. We suggest all future Phase 3 HIV vaccine trials conducted in helminth-endemic areas should incorporate standard diagnostic assays for helminth infections. Topic Categories Vaccines and Immunotherapy (VAC)