Immunogenicity of a chimeric Plasmodium falciparum merozoite surface protein vaccine in Aotus monkeys (original) (raw)
Related papers
2009
A chimeric gene, MSP-Fu24, was constructed by genetically coupling immunodominant, conserved regions of the two leading malaria vaccine candidates, Plasmodium falciparum merozoite surface protein 1 (C-terminal 19-kDa region [PfMSP-119]) and merozoite surface protein 3 (11-kDa conserved region [PfMSP-311]). The recombinant MSP-Fu24 protein was produced in Escherichia coli cells and purified to homogeneity by a two-step purification process with a yield of ∼30 mg/liter. Analyses of conformational properties of MSP-Fu24 using PfMSP-119-specific monoclonal antibody showed that the conformational epitopes of PfMSP-119 that may be critical for the generation of the antiparasitic immune response remained intact in the fusion protein. Recombinant MSP-Fu24 was highly immunogenic in mice and in rabbits when formulated with two different human-compatible adjuvants and induced an immune response against both PfMSP-119 and PfMSP-311. Purified anti-MSP-Fu24 antibodies showed invasion inhibition o...
Infection and Immunity, 2013
ABSTRACTThe C-terminal 19-kDa domain ofPlasmodium falciparummerozoite surface protein 1 (PfMSP119) is an established target of protective antibodies. However, clinical trials ofPfMSP142, a leading blood-stage vaccine candidate which contains the protective epitopes ofPfMSP119, revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in thePlasmodium yoeliimurine model, we produced a chimeric vaccine antigen containing recombinantPfMSP119(rPfMSP119) fused to the N terminus ofP. falciparummerozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (ΔAsn/Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (ΔAsn/Asp) fusion partner. While specific forPfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to bothPfMSP119and rPfMSP8 (ΔAsn/Asp) components. This occurred with formulations adjuva...