A single gene copy merozoite surface antigen and immune evasion?
During the course of chronic malaria infection antigenic variants of a parasite antigen are expressed and exposed on the surface of infected erythrocyte membranes. There also exists a number of apparently invariant single gene copy blood-stage antigens, exposed or non-exposed, which have been shown to afford immunity under experimental conditions. To determine why the host, presented with invariant 'protective' antigens, is unable to control infections effectively, immunity to a representative single gene copy antigen, the merozoite surface protein 1 (MSP1) was investigated in Plasmodium chabaudi chabaudi AS, a murine model of chronic malaria. Immunization with monoclonal antibody affinity purified native MSP1 resulted in enhanced control of parasitaemia on challenge, irrespective of the parasite inoculum size; challenge with a single parasite, however, suggested that expansion of resistant parasite subpopulations was not occurring. Challenge of mice immunized with recombinant fusion proteins encoding N- or C-terminal regions of the P.c. chabaudi AS MSP1 produced inconsistent effects, often parasitaemias were indistinguishable from controls despite significant anti-MSP1 antibody responses. The not unlikely contamination of MSP1 native preparations with erythrocyte (E) components was considered. Immunization with a mixture of the MSP1 C-terminus recombinant polypeptide and a Triton X-100 solubilized lysate of normal E resulted in enhanced control of parasitaemia, however, no effect was seen after administration of either component on its own. Co-immunization of E with the N-terminus polypeptide reversed the inhibition seen, on this occasion with this construct alone.
O'Dea
K P
KP
Division of Parasitology, National Institute for Medical Research, London, UK.
McKean
P G
PG
Jarra
W
W
Brown
K N
KN
D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D017125:Genes, Protozoan; D007114:Immunization; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D008297:Male; D020066:Merozoite Surface Protein 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018512:Parasitemia / Q000276:immunology; D016788:Plasmodium chabaudi / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013997:Time Factors
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; D011994:Recombinant Proteins