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Plasmodium Falciparum Merozoite Surface Protein 1 (MSP-1)-MSP-3 Chimeric Protein: Immunogenicity Determined With Human-Compatible Adjuvants and Induction of Protective Immune Response

Plasmodium Falciparum Merozoite Surface Protein 1 (MSP-1)-MSP-3 Chimeric Protein: Immunogenicity Determined With Human-Compatible Adjuvants and Induction of Protective Immune Response

Suman Mazumdar, Paushali Mukherjee, Syed Shams Yazdani, S K Jain, Asif Mohmmed, Virander Singh Chauhan

Infect Immun. 2010 Feb;78(2):872-83.

PMID: 19933832

Abstract:

A chimeric gene, MSP-Fu(24), 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-1(19)]) and merozoite surface protein 3 (11-kDa conserved region [PfMSP-3(11)]). The recombinant MSP-Fu(24) protein was produced in Escherichia coli cells and purified to homogeneity by a two-step purification process with a yield of approximately 30 mg/liter. Analyses of conformational properties of MSP-Fu(24) using PfMSP-1(19)-specific monoclonal antibody showed that the conformational epitopes of PfMSP-1(19) that may be critical for the generation of the antiparasitic immune response remained intact in the fusion protein. Recombinant MSP-Fu(24) was highly immunogenic in mice and in rabbits when formulated with two different human-compatible adjuvants and induced an immune response against both PfMSP-1(19) and PfMSP-3(11). Purified anti-MSP-Fu(24) antibodies showed invasion inhibition of P. falciparum 3D7 and FCR parasites, and this effect was found to be dependent on antibodies specific for the PfMSP-1(19) component. The protective potential of MSP-Fu(24) was demonstrated by in vitro parasite growth inhibition using an antibody-dependent cell inhibition (ADCI) assay with anti-MSP-Fu(24) antibodies. Overall, the antiparasitic activity was mediated by a combination of growth-inhibitory antibodies generated by both the PfMSP-1(19) and PfMSP-3(11) components of the MSP-Fu(24) protein. The antiparasitic activities elicited by anti-MSP-Fu(24) antibodies were comparable to those elicited by antibodies generated with immunization with a physical mixture of two component antigens, PfMSP-1(19) and PfMSP-3(11). The fusion protein induces a protective immune response with human-compatible adjuvants and may form a part of a multicomponent malaria vaccine.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1820968635	MSP-3		1820968-63-5	Price

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