Drexel University College of Medicine

Microbiology and Immunology Graduate Program BED, Biology and Chemistry Egerton University, Kenya M.S. Biology East Stroudsburg University, PA Email: james.randiak.alaro@drexel.edu Advisor: Dr. James Burns

Thesis Research Summary:

The search for an effective malaria vaccine continues with the most feasible vaccine against blood stage malaria aimed at inducing neutralizing antibodies against extracellular merozoites. Currently, inhibitory antibodies targeting membrane-associated merozoite surface protein 1 (MSP-1) antigens (the lead vaccine candidate) confer a level of immunity to Plasmodium falciparum, the most lethal of all malaria species. The great promise of recombinant Pf MSP-1 vaccine is however dampened by (1) the polymorphism mainly associated with T cell epitopes important in protection; (2) the less than optimal immunogenicity; and (3) the availability of other compensatory or redundant RBC invasion pathways. It is therefore apparent that a multi-subunit based vaccine will be most desirable. To improve the efficacy and immunogenicity of Pf MSP-1 based vaccine, we focus on another merozoite surface protein, MSP-8. Unlike Pf MSP-1, Pf MSP-8 is highly conserved throughout the protein sequence. Our main goal is to design a chimeric Pf MSP-1/MSP-8 antigen aimed at providing strong, conserved, plasmodial-specific CD4+ T cell epitopes to promote the production of antibodies to protective B cell epitopes of MSP-1 and MSP-8, including those associated with the functionally related C-terminal epidermal growth factor (EGF)-like domains present in the two proteins. In the short term, my research is focused on the identification of optimal MSP-8 fusion partner that will then be fused to the 19 kDa C-terminal portion of MSP-1 against which protective antibodies are made. We will then evaluate the quality and quantity of antibodies induced by immunization with this chimeric antigen. In the long term, we aim to design, produce, and test a bi-allelic formulation of the chimeric vaccine that will elicit high titers of antibodies able to neutralize merozoites of the two main P. falciparum strains, 3D7 and FVO.