Recombinant Plasmodium berghei merozoite surface protein-1 expressed in Salmonella: Evaluation of immunogenicity in a rodent model
Description
Oral vaccination with recombinant Salmonella effectively stimulates antibody and cellular responses against both the Salmonella carrier and heterologous antigen. Vaccination by the oral route is an especially attractive feature due to ease of administration and cost-effectiveness. This study explored the potential of such a strategy in the development of malarial vaccines. Recombinant DNA constructs expressing a region of Plasmodium berghei merozoite surface protein-1 as a fusion protein with the Escherichia coli proteins, maltose binding protein and B subunit of heat-labile enterotoxin were developed. Vaccination of outbred mice with the purified fusion protein in Freund's adjuvant and SDS-PAGE gel slices elicited a specific IgG antibody response against PbMSP-1 as determined by immunoblotting and an immunofluorescence assay. The fusion proteins were expressed in Salmonella and used to orally vaccinate mice. Vaccinated mice were challenged with P. berghei (NK65 strain) blood-stage parasites and monitored for parasitemia and protection. In all cases where mice were immunized with PbMS P-1 fusion proteins, some animals survived challenge without developing parasitemia. All control mice became patent and succumbed to challenge infection. This survival pattern was consistent regardless of the adjuvant used or if fusion proteins were administered in Salmonella. Antibody responses to PbMSP-1 did not always correlate with protection. Serum collected pre-challenge from mice immunized with recombinant Salmonella revealed either low or no antibody responses to PbMSP-1 suggesting that cellular mechanisms may be important for the degree of protection observed which may be potentiated by the Salmonella carrier. In conclusion, the present study has demonstrated that this region of PbMSP-1 is immunogenic and contains epitopes which probably contribute to a protective immune response against this molecule