Next generation sequencing to detect variation in the Plasmodium falciparum circumsporozoite protein.


Journal Article

The malaria vaccine RTS,S/AS01, based on immunogenic regions of the Plasmodium falciparum circumsporozoite protein (CSP), has partial efficacy against clinical malaria in African children. Understanding how sequence diversity in CSP T- and B-cell epitopes relates to naturally acquired and vaccine-induced immunity may be useful in efforts to improve the efficacy of CSP-based vaccines. However, limitations in sequencing technology have precluded thorough evaluation of diversity in the immunogenic regions of this protein. In this study, 454, a next generation sequencing technology, was evaluated as a method for assessing diversity in these regions. Portions of the circumsporozoite gene (cs) were sequenced both by 454 and Sanger sequencing from samples collected in a study in Bandiagara, Mali. 454 detected more single nucleotide polymorphisms and haplotypes in the T-cell epitopes than Sanger sequencing, and it was better able to resolve genetic diversity in samples with multiple infections; however, it failed to generate sequence for the B-cell epitopes.

Full Text

Duke Authors

Cited Authors

  • Gandhi, K; Thera, MA; Coulibaly, D; Traoré, K; Guindo, AB; Doumbo, OK; Takala-Harrison, S; Plowe, CV

Published Date

  • May 2012

Published In

Volume / Issue

  • 86 / 5

Start / End Page

  • 775 - 781

PubMed ID

  • 22556073

Pubmed Central ID

  • 22556073

Electronic International Standard Serial Number (EISSN)

  • 1476-1645

Digital Object Identifier (DOI)

  • 10.4269/ajtmh.2012.11-0478


  • eng

Conference Location

  • United States