Pre-Erythrocytic-Stage Vaccines
Pre-erythrocytic-stage vaccines are designed to induce immunity against antigens on sporozoites inoculated by mosquitoes to prevent invasion of human hepatocytes by sporozoites, or to prevent the development of a single sporozoite into thousands of individual merozoites in human hepatocytes. An effective pre-erythrocytic vaccine will thus prevent the clinical disease and also disrupt malaria transmission. Even a partially effective vaccine will significantly reduce the initial sporozoite and liver-stage parasite burden, thus leading to a substantial reduction in frequency and severity of clinical malaria.
CS Protein Vaccine
The MVDB added CSP to its Product Development Plan in October 2006. Our approach is to produce a recombinant protein encompassing the full-length CSP excluding the N-terminal signal and C-terminal GPI anchor signal sequences. The rationale for this approach is that the N-terminal segment of the CSP, including the conserved Region I, may also provide protective immunity. RTS,S contains half of the natural CS repeats without NVDP sequences, whereas our rCSP will include a complete repeat region. Moreover, the rCSP will be chemically conjugated to a recombinant P. aeruginosa rEPA to enhance the immunogenicity of the rCSP. This carrier has been used as the polysaccharide vaccine Vi against S. typhi, to improve the immunogenicity of the polysaccharide, and the conjugate vaccine is safe in humans and has been licensed in 94 countries. In the past few years, we have developed expertise in chemically conjugating malaria antigens, including AMA1, MSP1, MSP3, Pfs25H, Pvs25H and Pvs25, to this carrier. Conjugation significantly enhanced immunogenicity of these malaria antigens in animal studies. In addition, the Pfs25H-OMPC and Pfs25H-Pfs25H, conjugates that we have developed were capable of inducing sustained high immune responses in animals. We will investigate whether the rEPA as the carrier will also induce sustained immune responses to malaria antigens including rCSP.
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