Antigen and adjuvant selection for a vaccine against urogenital schistosomiasis, Hematoshield

PROJECT SUMMARY Schistosomiasis, caused by parasitic helminths, remains a major global health problem currently affecting over 250 million people in 78 countries with an additional 800 million people at risk of infection. Schistosoma haematobium causes female genital schistosomiasis and urinary schistosomiasis resulting in bladder cancer if left untreated. S. haematobium infection often results in formation of lesions within the vaginal tract of women, often rendering them more susceptible to HIV coinfection. Since 2014, urogenital schistosomiasis is now being actively transmitted in Southern Europe, a region previously thought to be schistosomiasis-free. Over the course of 20 years, we have developed a potent schistosomiasis vaccine for S. mansoni, termed SchistoShield®, targeting a functionally important antigen, Sm-p80, formulated using the TLR4-targeting adjuvant GLA-SE. SchistoShield® has been exhaustively tested in numerous animal models and has consistently exhibited protection at all parasite life cycle stages. We are near completion of a Phase 1 safety and dose-ranging human clinical trial with SchistoShield® in the US – with no safety signals reported – and will begin Phase 1B trials in Africa in Q3 of 2023 with a future Phase 2 trial in Africa to be funded by the Gates Foundation. We hypothesize that a Sh-p80-based vaccine for S. haematobium (HematoShieldTM) could be developed using our extensive experience with SchistoShield®, and that this homologous vaccine will provide superior protection against urogenital schistosomiasis. In this STTR we propose two Aims: (1) produce and release vaccine candidates and then to (2) Evaluate the vaccine candidates in an animal model of urogenital schistosomiasis. Successful completion of these Aims will be crucial identifying which candidate vaccine for this burdensome disease will be progressed into future current Good Manufacturing Practice (cGMP) production, stability, potency, and toxicology testing as well as important clinical trials for efficacy against S. haematobium.