Functional conservation of the malaria vaccine antigen MSP-1(19) across distantly related Plasmodium species

The C-terminal region of Plasmodium falciparum merozoite surface protein 1 (MSP-1(19)) is at present a leading malaria vaccine candidate. Antibodies a gainst the epidermal growth factor-like domains of MSP-1(19) are associated with immunity to P. falciparum(1-4) and active immunization with recombina nt forms of the molecule protect against malaria challenge in various exper imental systems(5-8), These findings, with the knowledge that epidermal gro wth factor-like domains in other molecules have essential binding functions , indicate the importance of this protein in merozoite invasion of red bloo d cells. Despite extensive molecular epidemiological investigations, only l imited sequence polymorphism has been identified in P. falciparum MSP-1(19) (refs, 9-11). This indicates its sequence is functionally constrained, and is used in support of the use of MSP-1(19) as a vaccine. Here, we have suc cessfully complemented the function of most of P. falciparum MSP-1(19) with the corresponding but highly divergent sequence from the rodent parasite P . chabaudi. The results indicate that the role of MSP-1(19) in red blood ce ll invasion is conserved across distantly related Plasmodium species and sh ow that the sequence of P. falciparum MSP-1(19) is not constrained by funct ion.