A Malaria Vaccine Based on the Polymorphic Block 2 Region of MSP-1 that Elicits a Broad Serotype-Spanning Immune Response

Graeme J. M. Cowan, Alison M. Creasey, Kelwalin Dhanasarnsombut, Alan W. Thomas, Edmond J. Remarque, David R. Cavanagh

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and expressed in E. coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody responses found among immune and semi-immune individuals in malaria endemic areas. The target population for such a vaccine is young children and vulnerable adults, to accelerate the acquisition of a full range of malaria protective antibodies against this polymorphic parasite antigen.

Original languageEnglish
Article numbere26616
Pages (from-to)-
Number of pages14
JournalPLoS ONE
Volume6
Issue number10
DOIs
Publication statusPublished - 26 Oct 2011

Keywords / Materials (for Non-textual outputs)

  • MEROZOITE SURFACE PROTEIN-1
  • INTRINSICALLY UNSTRUCTURED PROTEINS
  • PLASMODIUM-FALCIPARUM MALARIA
  • MEMBRANE ANTIGEN-1 AMA1
  • GLUTAMATE-RICH PROTEIN
  • ANTIBODY-RESPONSES
  • CLINICAL MALARIA
  • CELLULAR-INHIBITION
  • SEQUENCE DIVERSITY
  • SINGLE PROTEIN

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