Evidence for strain-specific protective immunity against blood-stage parasites of Plasmodium cynomolgi in toque monkey.

We have conducted experiments to test the induction of strain-specific protective immunity against Plasmodium cynomolgi infections in toque monkeys. Plasmodium cynomolgi is closely related biologically and genetically to the human malaria parasite, P. vivax. Two groups of monkeys were immunized against either of two strains of P. cynomolgi, namely PcCeylon and Pc746, by giving two successive drug-cured infections with asexual blood-stage parasites of one or the other strain, 12-weeks apart. To test for strain-specific protective immunity these infection-immunized monkeys were challenged 8 weeks later with a mixture of asexual blood-stage parasites of both strains. A pyrosequencing-based assay was used to quantify the proportion of parasites that survived in the challenge infections. The assay was based on a SNP within the P. cynomolgi Merozoite Surface Protein-1 gene. Compared to their behaviour in nonimmunized monkeys, the growth of parasites of the homologous (immunizing) strain in mixed-strain challenge infections in the immunized monkeys were reduced relative to that of the nonimmunizing strain. These results indicate the development of blood infection-induced strain-specific protective immunity against P. cynomolgi in toque monkeys. The work prepares for using genetic analysis to identify target antigens of strain-specific protective immunity in this host and malaria parasite combination.