A merozoite vaccine effective against Plasmodium knowlesi malaria

Abstract

Plasmodium knowlesi malaria is uniformly fatal in rhesus monkeys¹. If infections are initially controlled with drug therapy, however, a degree of immunity can be induced associated with periodic relapse and low grade infection after repeated challenge. In such resistant monkeys each recurring infection is attributable to a distinct parasite variant recognisable by the schizont-infected cell agglutination (SICA) test². Antigenic variation therefore seems to be an important mechanism determining chronicity of infection³ and complicates any attempt to achieve effective immunoprophylaxis⁴. Rhesus monkeys have been vaccinated with formol-treated^5,6 or freeze-thawed⁷ erythrocytic schizonts of P. knowlesi or fractions of these parasites^8,9 in complete (FCA) or incomplete (FIA) Freund's adjuvant. Such vaccination reduced mortality to about 50% after challenge with the homologous variant; in surviving monkeys parasitaemia reached 3–10%, but parasites were completely eliminated after about 2 weeks and some animals were then resistant to heterologous challenge⁷. When the first challenge variant was known to differ from that used for immunisation, all monkeys suffered fatal infections⁷. The protection achieved always required the use of complete adjuvant, but this alone was inactive.