Antibody-mediated functional responses induced by the SchistoShield® schistosomiasis vaccine in disease-naïve and endemic human populations

Résumé fourni par la source

Schistosomiasis (bilharzia) is a neglected tropical disease caused by Schistosoma spp. Clinical manifestation of chronic schistosomiasis include but not restricted to anemia, growth stunting, hepatosplenomegaly, cognitive impairment in children and male/female genital schistosomiasis. Praziquantel (PZQ) remains the principal standard treatment for schistosomiasis, but concerns about its reduced effectiveness against larval stages, reinfections, and emerging drug resistance reinforces the urgent 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 the USA and two countries in Africa (Madagascar and Burkina Faso). In this study, SchistoShield® vaccine specific total IgG antibody titers were measured from serum samples collected at multiple time points from both the USA and Africa trials. Results demonstrate that total IgG titers increased at week 5 after the first booster and peaked at weeks 9 and 12. Furthermore, in vitro schistosomula killing assays and heterologous passive transfer of purified total IgG in mice were performed to evaluate the role of vaccine-induced antibodies against schistosomes. Sera collected from individuals enrolled in the USA, Burkina Faso, and Madagascar trials, exhibited 69.2%, 55.1%, and 34.3% in vitro schistosomula killing, respectively, indicative of potent anti-worm antibody responses. Passive transfer of human total IgG from vaccinated individuals 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 generation of functional antibodies that may play a crucial role in antibody-mediated protection against schistosomiasis.