Synergistic malaria vaccine combinations identified by systematic antigen screening

Leyla Y. Bustamante, Gareth T. Powell, Yen Chun Lin, Michael D. Macklin, Nadia Cross, Alison Kemp, Paula Cawkill, Theo Sanderson, Cecile Crosnier, Nicole Muller-Sienerth, Ogobara K. Doumbo, Boubacar Traore, Peter D. Crompton, Pietro Cicuta, Tuan M. Tran, Gavin J. Wright, Julian C. Rayner

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.

Original languageEnglish (US)
Pages (from-to)12045-12050
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number45
DOIs
StatePublished - Nov 7 2017

Keywords

  • Antigen combinations
  • Erythrocyte invasion
  • Malaria
  • Plasmodium falciparum
  • Vaccine

ASJC Scopus subject areas

  • General

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  • Cite this

    Bustamante, L. Y., Powell, G. T., Lin, Y. C., Macklin, M. D., Cross, N., Kemp, A., Cawkill, P., Sanderson, T., Crosnier, C., Muller-Sienerth, N., Doumbo, O. K., Traore, B., Crompton, P. D., Cicuta, P., Tran, T. M., Wright, G. J., & Rayner, J. C. (2017). Synergistic malaria vaccine combinations identified by systematic antigen screening. Proceedings of the National Academy of Sciences of the United States of America, 114(45), 12045-12050. https://doi.org/10.1073/pnas.1702944114