Novel methods to expedite schistosome vaccine development

Abstract

This thesis explores novel methods to expedite schistosome vaccine development, particularly using controlled human infections. We describe the development of single-sex controlled human infection models (CHIMs) with Schistosoma mansoni using male or female cercariae. Both were dose-finding studies in which Schistosoma-naïve participants were exposed to pre-defined low doses (10, 20 or 30) of cercariae and followed-up over time to assess safety and infectivity. Given the potential influence of prior exposure to schistosomes, among others, on (vaccine) immune responses, we strongly encourage transfer of this CHIM to endemic settings. In support of this, we report on the potential risks related to implementing single-sex controlled human infection with schistosomes (CHI-S) in Uganda and provide mitigation strategies to minimise these risks. Next, we use the CHI-S to investigate whether repeated exposure and treatment leads to protection from reinfection and to identify potential correlates of protection or novel vaccine targets. In addition, we provide the study protocol for a CHI-S vaccine study to assess the protective efficacy of Sm-p80 + GLA-SE against controlled infection with male Schistosoma mansoni cercariae. Lastly, we reflect on immunological and methodological aspects of schistosomiasis vaccine development, especially when transitioning from phase II to phase III.