Genetic control of immunity to Plasmodium yoelii sporozoites.
Using a rodent malaria system, we have shown that protective immunity to the preerythrocytic stages of malaria is genetically controlled by MHC and non-MHC genes. Ten congenic strains of mice were immunized with irradiated sporozoites of Plasmodium yoelii. When challenged with viable sporozoites, only two strains had a high proportion of animals that did not develop blood stage infections. Immunity did not correlate with antisporozoite antibody levels. Two protective mechanisms exist determined by non-H-2 genes, and each mechanism is further controlled by H-2-linked Ir genes. On the BALB background only H-2d mice are protected, and protection is abolished by depleting CD8+ T cells. In contrast, on the B10 background only H-2q mice are strongly protected, and protection is not affected by CD8+ T cell depletion. If similar complex genetic regulation of immunity occurs in the human malarias, it will be a major hurdle for vaccine development.
Weiss
W R
WR
Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20814.
Good
M F
MF
Hollingdale
M R
MR
Miller
L H
LH
Berzofsky
J A
JA
D000818:Animals; D005787:Gene Frequency; D005802:Genes, MHC Class II; D006790:Host-Parasite Interactions; D007113:Immunity, Innate / Q000235:genetics*; D008288:Malaria / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D013045:Species Specificity