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. 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.
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References
Egan, A.F. et al. Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. J. Infect. Dis. 173, 765–769 (1996).
Blackman, M.J., Heidrich, H.-G., Donachie, S., McBride, J.S. & Holder, A.A. A single fragment of a malaria merozoite surface protein remains on the parasite during red blood cell invasion and is the target of invasion-inhibiting antibodies. J. Exp. Med. 172, 379–382 ( 1990).
Chang, S.P. et al. Regulation of antibody specificity to Plasmodium falciparum merozoite surface protein-1 by adjuvant and MHC haplotype. J. Immunol. 152, 3483–3490 (1994).
Egan, A., Burghaus, P., Druilhe, P., Holder, A. & Riley, E. Human antibodies to the 19kDa C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 inhibit parasite growth in vitro. Parasite Immunol. 21, 133–139 (1999).
Daly, T.M. & Long, C.A. A recombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice. Infect. Immun. 61, 2462–2467 (1993).
Ling, I.T., Ogun, S.A. & Holder, A.A. Immunization against malaria with a recombinant protein . Parasite Immunol. 16, 63– 67 (1994).
Rotman, H.L., Daly, T.M. & Long, C.A. Plasmodium: Immunization with carboxyl terminal regions of MSP-1 protects against homologous but not heterologous blood-stage parasite challenge. Exp. Parasitol. 91, 78– 85 (1999).
Perera, K.L., Handunnetti, S.M., Holm, I., Longacre, S. & Mendis, K. Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are highly protective in a natural primate model for human Plasmodium vivax malaria. Infect. Immun. 66, 1500–1506 ( 1998).
Kang, Y. & Long, C.A. Sequence heterogeneity of the C-terminal, Cys-rich region of the merozoite surface protein-1 (MSP-1) in field samples of Plasmodium falciparum. Mol. Biochem. Parasitol. 73, 103–110 (1995).
Miller, L.H., Roberts, T., Shahabuddin, M. & McCutchan, T.F. Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Mol. Biochem. Parasitol. 59, 1–14 (1993).
Qari, S.H. et al. Predicted and observed alleles of Plasmodium falciparum merozoite surface protein-1 (MSP-1), a potential malaria vaccine antigen . Mol. Biochem. Parasitol 92, 241– 252 (1998).
Blackman, M.J., Scott Finnigan, T.J., Shai, S. & Holder, A.A. Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein. J. Exp. Med. 180, 389– 393 (1994).
Cooper, J.A., Cooper, L.T. & Saul, A.J. Mapping of the region predominantly recognized by antibodies to the Plasmodium falciparum merozoite surface antigen MSA 1. Mol. Biochem. Parasitol. 51, 301– 312 (1992).
Chitarra, V., Holm, I., Bentley, G., Petres, S. & Longacre, S. The crystal structure of the C-terminal merozoite protein 1 at 1.8Å resolution, a highly protective malaria vaccine candidate. Mol. Cell. 3, 457–464 (1999).
Morgan, W. et al. Solution structure of the EGF module pair from the Plasmodium falciparum merozoite surface protein 1. J. Mol. Biol. 289, 113–122 (1999).
Egan, A.F. et al. Serum antibodies from malaria-exposed people recognize conserved epitopes formed by the two epidermal growth factor motifs of MSP-1(19), the carboxy-terminal fragment of the major merozoite surface protein of Plasmodium falciparum. Infect. Immun. 63, 456– 466 (1995).
Egan, A., Waterfall, M., Pinder, M., Holder, A. & Riley, E. Characterization of human T- and B-cell epitopes in the C terminus of Plasmodium falciparum merozoite surface protein 1: evidence for poor T-cell recognition of polypeptides with numerous disulfide bonds. Infect. Immun. 65, 3024 –3031 (1997).
Patino, J.A., Holder, A.A., McBride, J.S. & Blackman, M.J. Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies. J. Exp. Med. 186, 1689–1699 (1997).
Crabb, B.S., Triglia, T., Waterkeyn, J. & Cowman, A.F. Stable transgene gene expression in Plasmodium falciparum. Mol. Biochem. Parasitol. 90, 131–144 (1997).
Crabb, B.S. & Cowman, A.F. Characterization of promoters and stable transfection by homologous and nonhomologous recombination in Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 93, 7289–7294 (1996).
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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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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DOI: https://doi.org/10.1038/71595
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