Experimental vaccinology, revealing unnatural signatures of protection by repeat controlled human schistosome infection.

Schistosomiasis is a neglected tropical disease afflicting over 200 million people and causing 300,000 deaths in Africa alone. Whilst infections can be cleared with schistosomocidal drugs, individuals will become rapidly re-infected upon exposure to contaminated water. Partial immunity only develops naturally only after decades of constant infection, and there is no vaccine. Previous schistosome vaccine studies have been flawed, due to a lack of understanding of what constitutes a protective immune response, focus on single antigen targets, and a lack of pharmaceutical industry support or expertise for development.Here, I propose to use unique samples from repeat Schistosoma mansoni controlled human infection (Sm-CHI) models to reveal novel antigens and corresponding cellular and cytokine responses that are protective against schistosomiasis. To evaluate how well this protective signature will translate to endemic countries, matched analyses will be performed in samples from naturally schistosome infected Ugandan individuals. Antigen-specific antibody and cellular immunology data will be combined utilising bioinformatic tools to reveal a signature of multiple antigens and immune responses associated with protection from schistosomiasis. Next, in a non-academic placement at Batavia Biosciences, I will develop a pre-clinical development plan to translate the identified protective immune signature into an effective vaccine against human schistosomiasis. This fellowship will form the basis of my future career development, to become an independent researcher in the field of schistosome vaccinology.