Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development.


Journal Article

Vaccines directed against the blood stages of Plasmodium falciparum malaria are intended to prevent the parasite from invading and replicating within host cells. No blood-stage malaria vaccine has shown clinical efficacy in humans. Most malaria vaccine antigens are parasite surface proteins that have evolved extensive genetic diversity, and this diversity could allow malaria parasites to escape vaccine-induced immunity. We examined the extent and within-host dynamics of genetic diversity in the blood-stage malaria vaccine antigen apical membrane antigen-1 in a longitudinal study in Mali. Two hundred and fourteen unique apical membrane antigen-1 haplotypes were identified among 506 human infections, and amino acid changes near a putative invasion machinery binding site were strongly associated with the development of clinical symptoms, suggesting that these residues may be important to consider in designing polyvalent apical membrane antigen-1 vaccines and in assessing vaccine efficacy in field trials. This extreme diversity may pose a serious obstacle to an effective polyvalent recombinant subunit apical membrane antigen-1 vaccine.

Full Text

Duke Authors

Cited Authors

  • Takala, SL; Coulibaly, D; Thera, MA; Batchelor, AH; Cummings, MP; Escalante, AA; Ouattara, A; Traoré, K; Niangaly, A; Djimdé, AA; Doumbo, OK; Plowe, CV

Published Date

  • October 14, 2009

Published In

Volume / Issue

  • 1 / 2

Start / End Page

  • 2ra5 -

PubMed ID

  • 20165550

Pubmed Central ID

  • 20165550

Electronic International Standard Serial Number (EISSN)

  • 1946-6242

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.3000257


  • eng

Conference Location

  • United States