Genome-level determination of plasmodium falciparum blood-stage targets of malarial clinical immunity in the peruvian amazon

Katherine J. Torres, Carlos E. Castrillon, Eli L. Moss, Mayuko Saito, Roy Tenorio, Douglas M. Molina, Huw Davies, Daniel E. Neafsey, Philip Felgner, Joseph M. Vinetz, Dionicia Gamboa

Research output: Contribution to journalArticle

Abstract

Background Persons with blood-stage Plasmodium falciparum parasitemia in the absence of symptoms are considered to be clinically immune. We hypothesized that asymptomatic subjects with P. falciparum parasitemia would differentially recognize a subset of P. falciparum proteins on a genomic scale. Methods and Findings. Compared with symptomatic subjects, sera from clinically immune, asymptomatically infected individuals differentially recognized 51 P. falciparum proteins, including the established vaccine candidate PfMSP1. Novel, hitherto unstudied hypothetical proteins and other proteins not previously recognized as potential vaccine candidates were also differentially recognized. Genes encoding the proteins differentially recognized by the Peruvian clinically immune individuals exhibited a significant enrichment of nonsynonymous nucleotide variation, an observation consistent with these genes undergoing immune selection. Conclusions. A limited set of P. falciparum protein antigens was associated with the development of naturally acquired clinical immunity in the low-transmission setting of the Peruvian Amazon. These results imply that, even in a low-transmission setting, an asexual blood-stage vaccine designed to reduce clinical malaria symptoms will likely need to contain large numbers of often-polymorphic proteins, a finding at odds with many current efforts in the design of vaccines against asexual blood-stage P. falciparum.

Original languageEnglish (US)
Pages (from-to)1342-1351
Number of pages10
JournalJournal of Infectious Diseases
Volume211
Issue number8
DOIs
StatePublished - Apr 15 2015
Externally publishedYes

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Keywords

  • geographic medicine
  • immunology
  • malaria
  • systems biology

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Torres, K. J., Castrillon, C. E., Moss, E. L., Saito, M., Tenorio, R., Molina, D. M., Davies, H., Neafsey, D. E., Felgner, P., Vinetz, J. M., & Gamboa, D. (2015). Genome-level determination of plasmodium falciparum blood-stage targets of malarial clinical immunity in the peruvian amazon. Journal of Infectious Diseases, 211(8), 1342-1351. https://doi.org/10.1093/infdis/jiu614