Development of Pre-Erythrocytic Malaria Vaccines

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The major discovery this year are as follows. 1. Completed a phase II clinical trial in Kenya in 5-12 month infants to assess whether irradiated PfSPZ given by the IV route is safe, and confers durable immunity and protection against natural exposure. Immune responses are currently being assessed to understand why the vaccine had limited protection in this age group. 2. Isolated monoclonal antibodies against malaria specific proteins ( eg CSP) in vaccinated and protected subjects. Showed these antibodies were protective in vivo in two different mouse models. Defined a novel epitope on PfCSP which is the site of neutralization. A crystal structure of a human antibody was obtained binding to a specific and unique epitope on PfCSP. The data provide an antibody that can be advanced for prevention of malaria in humans and defines a novel site of vulnerability on PfCSP that can be advanced as a vaccine using structure based vaccine design. 3. Started a clinical development plan for mAB CIS 43 against the junctional region of CSP for testing in humans. 4. Defined a new human mAb with distinct specificity and increased potency compared to CIS 43. 5. Comparative analysis of the in vivo potency of a number of human mAbs against CSP. Elucidation of the in vivo mechanisms of these antibodies focused in skin and liver.