Protective immunity includes cooperation between two lymphocyte populations and macrophage activation, but parasites survive by frequent changes of certain antigens. Continued multiplication of other antigenic cells may involve similar antigenic variation.

Protective Immunity to Malaria provides a Model for the Survival of Cells in an Immunologically Hostile Environment

Immunity to malaria: I. Protection against Plasmodium knowlesi shown by monkeys sensitized with drug-suppressed infections or by dead parasites in Freund's adjuvant

Phagocytosis of merozoites and schizont-infected erythrocytes prepared from continuous cultures by peripheral blood monocytes from patients with falciparum malaria was investigated with an in vitro assay. Monocytes do ingest merozoites of Plasmodium falciparum, but rarely phagocytose parasitized or nonparasitized erythrocytes in the absence of immune serum. The monocytes from hyperimmune subjects were significantly more efficient in the ingestion of merozoites than were those obtained from sensitized or noninfected subjects. These data indicate, first, that the merozoite rather than the parasitized erythrocyte is the specific target for blood phagocytic cells in human falciparum malaria and, second, that the phagocytosis of merozoites by peripheral blood monocytes increases depending on the level of specific immunity.

Enhanced Plasmodium falciparum merozoite phagocytosis by monocytes from immune individuals.

Immunity to malaria: II. Serological response of monkeys sensitized by drug-suppressed infection or by dead parasitized cells in Freund's complete adjuvant

Malaria remains prevalent throughout tropical and subtropical regions and almost a third of the World's population is exposed to the risk of infection. There is currently a serious resurgence of the disease in Asia and Central America. The failure of global eradication measures based upon the use of insecticides and chemotherapy has resulted from difficulties of practical implementation compounded by the spread of insecticide and drug resistance. Repeated natural infection does not produce detectable resistance to the exo-erythrocytic cycle of malaria in man. Irradiated sporzoite vaccines do, however, induce stage specific immunity in murine malaria and in a proportion of human subjects. Vaccinated individuals remain susceptible to blood stage infection which causes clinical malaria. In addition the vaccine is unstable and must be administered by intravenous inoculation. Since neither sporogonic nor exo-erythrocytic parasite development is cyclical in human malarias, there is little prospect for vaccine production through cultivation of these stages. The inhabitants of hyperendaemic areas become increasingly resistant to malaria during childhood and adolescence, through the slow development of specific, acquired immunity to asexual blood stage parasites. Immunity is mediated by antibody, which blocks merozoite invasion of red cells, as well as by cell mediated mechanisms and non-specific cytotoxic agents. Vaccination with merozoites induces long lasting immunity of broad serological specificity active against the blood-stage of the parasite. Merozoite vaccines can be preserved by freeze drying and harvested from continuous cultures of blood stage parasites. The major problem in development of a human merozoite vaccine concerns the requirement for Freund's complete adjuvant which is not acceptable for man. The effective immunity induced by vaccination contrasts with the slow development of incomplete resistance which follows repeated natural infection. The latter is associated with the generation of immune suppressor cells, lymphoid cell mitogens and soluble antigens, and in some species by the occurrence of antigenic variation--all of which may favour parasite survival. It is probable that vaccination with non-viable antigen of appropriate composition, induces immune effector processes without activating mechanisms which allow parasites to escape the consequences of immunity. Many effective vaccines such as those against measles, poliomyelitis, tetanus and rabies are commercially available but barely used in the developing world. The affected nations cannot afford their purchase, nor do the means exist for their distribution. It follows that if a safe and effective malaria vaccine were to be developed, its bulk manufacture and administration would require massive international support and cooperation.

Immunity to malaria.

Immunity to malaria: III. Possible occurrence of a cell-mediated immunity to Plasmodium knowlesi in chronically infected and Freund's complete adjuvant-sensitized monkeys

D.C. Dumonde

Papers

Immunity to malaria: III. Possible occurrence of a cell-mediated immunity to Plasmodium knowlesi in chronically infected and Freund's complete adjuvant-sensitized monkeys

Immunity to malaria: studies with Plasmodium knowlesi.