Parasitic diseases cause considerable morbidity and mortality in poverty-stricken areas, affecting hundreds of millions of lives globally. Vaccines are urgently needed to alleviate disease and lift the economic consequences. Plasmodium falciparum malaria, Schistosoma mansoni and Necator americanus hookworms are together responsible for the greatest burden of disease. Vaccination with attenuated parasites is a successful strategy in inducing immunity to parasites in animal models. Recently, Roestenberg’s group has shown in proof-of-concept clinical trials that attenuated parasite vaccination in humans results in a high protection rate from challenge with wild type parasites. This unique data indicates a role for the skin as a prime immunological organ. Based on these findings, this project aims to create a next generation of highly immunogenic, adjuvanted whole parasite vaccines, ready for pre-clinical testing. Chemical tools will be developed to load whole parasites with adjuvants. To measure the immunogenicity of the new vaccines, tools need to be developed to measure early skin-based humoral and cellular immune markers which associate with protection. By making use of controlled human infection models, the functionality of antibodies will be assessed with novel molecular imaging tools to quantitatively analyze movement kinematics of parasites in representative 3D environments resembling the human skin. Cellular correlates of protection in skin will be mapped using imaging mass cytometry on freshly obtained skin biopsies from experimentally infected volunteers. In parallel high-dimensional flow cytometry will be used to analyze circulating immune markers. By integrating local and systemic immune profiles, this project takes a comprehensive approach to identify immune responses associated with protection. This high-risk high-gain project aims to break the impasse in the field of parasite vaccine development and open a novel out-of-the-box avenue to advance the vaccine pipeline.
