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.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Takala SL,Coulibaly D,Thera MA,Batchelor AH,Cummings MP,Escalante AA,Ouattara A,Traoré K,Niangaly A,Djimdé AA,Doumbo OK,Plowe CVdoi
10.1126/scitranslmed.3000257subject
Has Abstractpub_date
2009-10-14 00:00:00pages
2ra5issue
2eissn
1946-6234issn
1946-6242journal_volume
1pub_type
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