Principal Investigator (PI)
The Foundation is providing £147,121 in support.
Patricia dos Santos
GSK contribution to the project will include providing the humanized mouse models to be employed in the project, as well as the technical expertise, equipment and reagents to assess the parasite’s ability to infect and develop in human and mouse red blood cells. This project will synergize with ongoing efforts of the GSK-DDW group, as the liver stage of Plasmodium infection has been considered a strategy priority of the unit. A follow up of the successful open Lab TC111 is planned for 1Q19 in order to transfer and implement an optimized pseudo liver-mouse model.
Malaria remains the most prevalent parasitic disease for which a vaccine is still not available. So far, whole-sporozoite (Wsp) vaccines have shown most success among current candidates. The applicant’s lab has defined and established the proof-of-concept of a novel approach to Wsp malaria vaccination, based on the use of non-pathogenic rodent malaria parasites, genetically engineered to express antigens of their human-infective counterparts. PbVac, a Plasmodium berghei (Pb) parasite that expresses the P. falciparum (Pf) circumsporozoite protein is the first member of this new class of vaccine candidates. PbVac has demonstrated high safety profile and significant immunizing efficacy in recent phase I/IIa clinical trials. Stemming from these encouraging results, we now propose to generate and evaluate a new transgenic Pb parasite with enhanced immunogenicity and efficacy against Pf infection. To this end, we will engineer a Pb parasite line that expresses multiple antigens of the human-infective Pf parasite, we will characterize the expression of the inserted transgenes, and we will define its infectivity both in the mosquito vector and in the mammalian host. In order to ensure the safety and regulatory compliance of the newly generated Pb-based immunization agent, we will make use of GSK-DDW’s blood-humanized (BH) mouse model to pre-clinically assess lack of infection of human (Hu) red blood cells (RBC) by these parasites. This is a pivotal step in the definition of the parasite’s safety profile and a crucial requirement for the regulatory approval of its clinical use.