Induction of protective immunity against malaria by MSP1/hsc70 fusion protein vaccine

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We have developed a method to induce CD4 and CDS specific immune responses by immunizing mice with a particular antigen as a fusion partner of mouse heat-shock cognate protein 70 (hsc70). We used this strategy to induce protective immunity against malaria sporozoite infection. We generated a recombinant protein of MSP1 fused to hsc70 (MSP1/hsc70) and studied whether it could induce protective immunity against liver stage P. yoelii, since we found that MSP1 is expressed during liver stage of P. yoelii life cycle. The immunization of mice with MSP1/hsc70 without any additional adjuvant induced strong specific antibody responses and IFN-y production. When the immunized mice were challenged with P. yoelii sporozoites, the onset of parasitemia delayed a few days when compared with naive mice or mice immunized with hsc70 alone, suggesting the induction of protective immune responses against liver stage malaria. To confirm the MSP1-specific protective immune responses against exoerythrocytic forms of malaria infection, we performed RT-PCR analysis of P. yoelii-specific rRNA in the infected liver. The level of P. yoelii was reduced in mice immunized with this fusion protein, but not in mice immunized with hsc70 alone, suggesting that MSP1-specific protective immunity is effective at liver stage malaria. This protective immunity was transferred into naive mice by spleen cells or liver lymphocytes of immune mice but not by antiserum, indicating that the protection is mediated by cellular mechanisms. Finally, the vaccine-induced protection was observed in C57BL/6, A/J, BALB/c and C3H mice suggesting that MSP1-specific protective immunity at the exoerythrocytic stage can be induced in animals over a wide range of genetic backgrounds.