Antibody-mediated Functional Responses Induced by the SchistoShield® Schistosomiasis Vaccine in Disease-naïve and Endemic Human Populations

Schistosomiasis (bilharzia) is a persistent and debilitating neglected tropical disease caused by Schistosoma species. Common symptoms include Katayama fever, gastrointestinal issues, and hematuria. Praziquantel (PZQ) is currently the only treatment available, but concerns about its reduced effectiveness against larval stages, reinfections, and emerging resistance highlight the need for a vaccine. SchistoShield®, composed of Sm-p80 antigen with GLA-SE adjuvant, is a promising vaccine candidate that has successfully completed Phase 1 and 1b clinical trials in disease-naïve populations in the US and endemic regions in Madagascar and Burkina Faso. In this study, we measured the total IgG antibody titers specific to Sm-p80 from serum samples collected at multiple time points from both trials. Additionally, functional assays evaluated the role of vaccine-induced antibodies against schistosomes including in vivo schistosomula killing and heterologous passive transfer of purified IgG from volunteers in the trials. We demonstrated a significant rise in total IgG titers at week 5 after the first booster, and another rise that peaked at week 12 (28 days after the second booster). Sera from US, Burkina Faso, and Madagascar vaccinated individuals supplemented with exogenous complement exhibited 69%, 55%, and 33% in vivo schistosomula killing, respectively demonstrating potent anti-worm antibody responses. Passive transfer experiments in mice revealed notable reductions in worm burden, egg counts, and egg-hatching ability compared to groups given pre-vaccination sera across all trials. Overall, these findings support that SchistoShield® induces functional antibodies targeting Sm-p80 which will play a crucial role in antibody-mediated protection against schistosomiasis.