Merozoite vaccination against Plasmodium knowlesi malaria

Abstract

Free malarial merozoites isolated from in vitro cultures of P. knowlesi and emulsified with Freund's complete (FCA) or incomplete (FIA) adjuvant were used to vaccinate twelve Rhesus monkeys against the uniformly lethal infection caused by P. knowlesi. Initial challenge of six monkeys with the same parasite variant as used for vaccination produced no detectable infection in three monkeys, while three others developed low-grade parasitaemia (maximum 1.5 per cent), which terminated after 6-11 days. Vaccination with merozoites in either FCA or FIA induced protection against homologous variant challenge. Six other monkeys were challenged first with a parasite variant different from that used for vaccination. Two animals immunized with merozoites in FIA alone or in FCA on only one occasion developed fatal infections. The other four animals vaccinated at least twice with merozoites in FCA showed low-grade parasitaemia (maximum 1.5 per cent) which terminated after 8-12 days. Eight monkeys rechallenged on eleven occasions at intervals of up to 16 weeks were completely resistant to several variants and a distinct laboratory strain of P. knowlesi, but developed chronic malaria similar to that in unimmunized controls when challenged with a different species of malaria, P. cynomolgi bastianellii. It is concluded that merozoite vaccination of Rhesus monkeys induces immunity against the erythrocyte stages of P. knowlesi far greater in degree and significantly broader in variant specificity than that achieved by previous methods of immunization or by repeated drug-controlled infections.