One of the most difficult obstacles faced in the development of a malaria vaccine is to overcome the ability of the parasite to misdirect immune responses away from the critical protective epitopes. Overcoming problems associated with misdirected immune responses and antigenic diversity may be extremely important in making a malaria vaccine possible. Clinical symptoms of malaria are associated with asexual multiplication of merozoites within erythrocytes. Unlike sporozoite based vaccines which render the host infection free, the goal of a merozoite vaccine is to render patients clinically asymptomatic. The long term objective of this proposal is to develop and commercialize an erythrocyte stage MSP1-42 malaria vaccine against P. falciparum. The malaria merozoite protein MSP-1 is proteolytically cleaved to MSP-33 and MSP-19. The immune response to tp MSP-1 in mice and humans elicits both protective (proteolytic inhibiting-Iab) and parasite enhancing (blocking antibodies-Babs). Babs interfere with the with the protective immunity of Iabs through stearic hindrance on the MSP1 protein. This study proposes to enhance the protective efficacy of a MSP-1 as a vaccine by turning down the immune responses to the protective Iab domain. Phase I will involve mapping the immune dampening of Bab epitopes on MSP1-42. Modified recombinant proteins will be expressed in E. coli and tested for the loss of Bab binding while still retaining the ability to bind Iabs.
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