title: Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development.
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.
authors.affiliation: Howard Hughes Medical Institute and Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Takala
authors.forename: Drissa
authors.initials: D
authors.lastname: Coulibaly
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Batchelor
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cummings
authors.forename: Ananias A
authors.initials: AA
authors.lastname: Escalante
authors.forename: Amed
authors.initials: A
authors.lastname: Ouattara
authors.forename: Karim
authors.initials: K
authors.lastname: Traoré
authors.forename: Amadou
authors.initials: A
authors.lastname: Niangaly
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimdé
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D017780:Malaria Vaccines / Q000009:adverse effects / Q000235:genetics*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008302:Mali; D010963:Plasmodium falciparum / Q000276:immunology; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines