Functional conservation of the malaria vaccine antigen MSP-119across distantly related Plasmodium species

Abstract

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-119are associated with immunity to P. falciparum1,2,3,4 and active immunization with recombinant forms of the molecule protect against malaria challenge in various experimental systems5,6,7,8. 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. 911). 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.

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Figure 1: Plasmids and integration events after transfection into P. falciparum parasites.
Figure 3: Phenotypic analyses of transfected parasite lines.
Figure 2: Sequence of the MSP-1 chimera and growth characteristics of parasites expressing this molecule.

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Acknowledgements

We thank R. Anders and D. Roos for advice; Y.Z. Zheng for generating the MSP-119 pFLAG plasmid; and T. Byrne for technical assistance. This work was supported by the National Health and Medical Research Council of Australia. R.A.O. is the recipient of an Australian Postgraduate Research Award.

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Correspondence to Brendan S. Crabb.

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O'Donnell, R., Saul, A., Cowman, A. et al. Functional conservation of the malaria vaccine antigen MSP-119across distantly related Plasmodium species. Nat Med 6, 91–95 (2000). https://doi.org/10.1038/71595

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