Extreme polymorphism in a vaccine antigen and risk of clinical malaria

Implications for vaccine development

Shannon L. Takala, Drissa Coulibaly, Mahamadou A. Thera, Adrian H. Batchelor, Michael P. Cummings, Ananias A. Escalante, Amed Ouattara, Karim Traoré, Amadou Niangaly, Abdoulaye A. Djimdé, Ogobara K. Doumbo, Christopher V. Plowe

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number2ra5
JournalScience Translational Medicine
Volume1
Issue number2
DOIs
StatePublished - Oct 14 2009

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Malaria Vaccines
Vaccines
Antigens
Parasites
Membranes
Mali
Falciparum Malaria
Haplotypes
Malaria
Longitudinal Studies
Immunity
Membrane Proteins
Binding Sites
Amino Acids
Infection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Takala, S. L., Coulibaly, D., Thera, M. A., Batchelor, A. H., Cummings, M. P., Escalante, A. A., ... Plowe, C. V. (2009). Extreme polymorphism in a vaccine antigen and risk of clinical malaria: Implications for vaccine development. Science Translational Medicine, 1(2), [2ra5]. https://doi.org/10.1126/scitranslmed.3000257

Extreme polymorphism in a vaccine antigen and risk of clinical malaria : Implications for vaccine development. / Takala, Shannon L.; Coulibaly, Drissa; Thera, Mahamadou A.; Batchelor, Adrian H.; Cummings, Michael P.; Escalante, Ananias A.; Ouattara, Amed; Traoré, Karim; Niangaly, Amadou; Djimdé, Abdoulaye A.; Doumbo, Ogobara K.; Plowe, Christopher V.

In: Science Translational Medicine, Vol. 1, No. 2, 2ra5, 14.10.2009.

Research output: Contribution to journalArticle

Takala, SL, Coulibaly, D, Thera, MA, Batchelor, AH, Cummings, MP, Escalante, AA, Ouattara, A, Traoré, K, Niangaly, A, Djimdé, AA, Doumbo, OK & Plowe, CV 2009, 'Extreme polymorphism in a vaccine antigen and risk of clinical malaria: Implications for vaccine development', Science Translational Medicine, vol. 1, no. 2, 2ra5. https://doi.org/10.1126/scitranslmed.3000257
Takala, Shannon L. ; Coulibaly, Drissa ; Thera, Mahamadou A. ; Batchelor, Adrian H. ; Cummings, Michael P. ; Escalante, Ananias A. ; Ouattara, Amed ; Traoré, Karim ; Niangaly, Amadou ; Djimdé, Abdoulaye A. ; Doumbo, Ogobara K. ; Plowe, Christopher V. / Extreme polymorphism in a vaccine antigen and risk of clinical malaria : Implications for vaccine development. In: Science Translational Medicine. 2009 ; Vol. 1, No. 2.
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