Antigenic variation and protective immunity in Plasmodium knowlesi malaria

Rhesus monkeys were immunized with defined strains and variants of Plasmodium knowlesi and their immunity on challenge was correlated with serum levels of schizont agglutinins and specific inhibitory antibody assayed by in vitro parasite culture. The results indicate that the inhibitory antibody provides a consistent index of immune status and probably represents the protective antibody which initiates specific immune reactions in vivo. The relationship between inhibitory and schizont agglutinating antibodies is discussed.

Inhibitory antibody is predominantly specific for those variants which have produced patent infections. However, antibody active against other variants is also present at lower titre and is associated with clinical immunity on challenge with such variants. The presence of this antibody could explain why P. knowlesi parasites, which arise by antigenic variation during the course of a chronic infection, produce mild parasitaemia in the host and yet are fully virulent in normal monkeys.

The occurrence of cross-immunization between variants and between some strains of P. knowlesi is encouraging from the point of view of malaria vaccine production. A preparation containing common antigens may induce a degree of clinical immunity comparable with that appearing during the course of chronic infection.