Functional conservation of the malaria vaccine antigen MSP-119across distantly related Plasmodium species.
The C-terminal region of Plasmodium falciparum merozoite surface protein 1 (MSP-119) is at present a leading malaria vaccine candidate. Antibodies against the epidermal growth factor-like domains of MSP-1 19are associated with immunity to P. falciparum and active immunization with recombinant forms of the molecule protect against malaria challenge in various experimental systems. These findings, with the knowledge that epidermal growth factor-like domains in other molecules have essential binding functions, indicate the importance of this protein in merozoite invasion of red blood cells. Despite extensive molecular epidemiological investigations, only limited sequence polymorphism has been identified in P. falciparum MSP-119 (refs. 9-11). This indicates its sequence is functionally constrained, and is used in support of the use of MSP-119 as a vaccine. Here, we have successfully complemented the function of most of P. falciparum MSP-119 with the corresponding but highly divergent sequence from the rodent parasite P. chabaudi. The results indicate that the role of MSP-119 in red blood cell invasion is conserved across distantly related Plasmodium species and show that the sequence of P. falciparum MSP-119 is not constrained by function.
O'Donnell
R A
RA
Department of Microbiology, The University of Melbourne, Parkville, Victoria 3052, Australia.
Saul
A
A
Cowman
A F
AF
Crabb
B S
BS
D000595:Amino Acid Sequence; D000818:Animals; D004912:Erythrocytes / Q000469:parasitology; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D011739:Pyrimethamine / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011739:Pyrimethamine