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Kirsten E Lyke

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

Kavita Gandhi; Mahamadou A Thera; Drissa Coulibaly; Karim Traoré; Ando B Guindo; Ogobara K Doumbo; Shannon Takala-Harrison; Christopher V Plowe (Profiled Author: Christopher Plowe)

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. Kavita.Gandhi@som.umaryland.edu
The American journal of tropical medicine and hygiene 2012;86(5):775-81.

Abstract

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.

10 Originating Grant

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