Use of massively parallel pyrosequencing to evaluate the diversity of and selection on plasmodium falciparum csp T-cell epitopes in Lilongwe, Malawi

Jeffrey A. Bailey, Tisungane Mvalo, Nagesh Aragam, Matthew Weiser, Seth Congdon, Debbie Kamwendo, Francis Martinson, Irving Hoffman, Steven R. Meshnick, Jonathan J. Juliano

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The development of an effective malaria vaccine has been hampered by the genetic diversity of commonly used target antigens. This diversity has led to concerns about allele-specific immunity limiting the effectiveness of vaccines. Despite extensive genetic diversity of circumsporozoite protein (CS), the most successful malaria vaccine is RTS/S, a monovalent CS vaccine. By use of massively parallel pyrosequencing, we evaluated the diversity of CS haplotypes across the T-cell epitopes in parasites from Lilongwe, Malawi. We identified 57 unique parasite haplotypes from 100 participants. By use of ecological and molecular indexes of diversity, we saw no difference in the diversity of CS haplotypes between adults and children. We saw evidence of weak variant-specific selection within this region of CS, suggesting naturally acquired immunity does induce variant-specific selection on CS. Therefore, the impact of CS vaccines on variant frequencies with widespread implementation of vaccination requires further study.

Original languageEnglish (US)
Pages (from-to)580-587
Number of pages8
JournalJournal of Infectious Diseases
Volume206
Issue number4
DOIs
StatePublished - Aug 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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