Plasmodium falciparum merozoite surface protein 1 (MSP-1)-MSP-3 chimeric protein: immunogenicity determined with human-compatible adjuvants and induction of protective immune response.
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.
Mazumdar
Suman
S
International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Mukherjee
Paushali
P
Yazdani
Syed Shams
SS
Jain
S K
SK
Mohmmed
Asif
A
Chauhan
Virander Singh
VS
D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000235:genetics*; D051379:Mice; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C089133:merozoite surface protein 3, Plasmodium