Antibody Induced Variation in Malaria Parasites

Abstract

SUCCESSFUL cellular differentiation and function are dependent upon responsiveness to external stimuli, both useful and harmful, and this responsiveness is particularly evident among some parasitic protozoa. Their environment changes abruptly at transmission from invertebrate vector to mammalian host and becomes potentially harmful when the host mounts an immune response. Several, and possibly most, protozoan parasites avoid total destruction by the immune response they evoke by repeated changes of antigenicity¹. Replacement of one population by another is detectable in tests carried out at weekly intervals^2,3, and variation at this rate apparently continues for months and perhaps even years. In the absence of suitable techniques for in vitro cultivation, the question remained whether this variation resulted from immunoselection or from a form of antigenic modulation. Here I have attempted to clarify this point with one species of malaria parasite, Plasmodium knowlesi, using an in vivo technique based upon earlier observations^4,5 that Macaca mulatta, sensitized with P. knowlesi antigen in incomplete Freund's adjuvant, produces high titres of variant-specific schizont-infected cell agglutinating antibodies which were not protective. Animals sensitized in this way were challenged with homologous parasites in numbers small enough to allow detection of possible immunoselection by delay in parasitaemia or failure in the appearance of a new antigenic variant. Results indicated that antigenic variation in P. knowlesi is non-selective and that potential for variation on this scale is an integral part of the parasite genome. Three experiments were carried out with similar results, and one is described here.