title: Use of massively parallel pyrosequencing to evaluate the diversity of and selection on Plasmodium falciparum csp T-cell epitopes in Lilongwe, Malawi.
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.
authors.affiliation: Division of Transfusion Medicine and Program in Bioinformatics and Integrative Biology, University of Massachusetts School of Medicine, Worcester, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bailey
authors.forename: Tisungane
authors.initials: T
authors.lastname: Mvalo
authors.forename: Nagesh
authors.initials: N
authors.lastname: Aragam
authors.forename: Matthew
authors.initials: M
authors.lastname: Weiser
authors.forename: Seth
authors.initials: S
authors.lastname: Congdon
authors.forename: Debbie
authors.initials: D
authors.lastname: Kamwendo
authors.forename: Francis
authors.initials: F
authors.lastname: Martinson
authors.forename: Irving
authors.initials: I
authors.lastname: Hoffman
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Juliano
mesh_terms: D000328:Adult; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology*; D008295:Malawi; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D016054:DNA, Protozoan; D018984:Epitopes, T-Lymphocyte; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan