Genome-level determination of Plasmodium falciparum blood-stage targets of malarial clinical immunity in the Peruvian Amazon.
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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. |
Year of Publication | 2015
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Journal | J Infect Dis
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Volume | 211
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Issue | 8
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Pages | 1342-51
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Date Published | 2015 Apr 15
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ISSN | 1537-6613
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URL | |
DOI | 10.1093/infdis/jiu614
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PubMed ID | 25381370
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PubMed Central ID | PMC4402338
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Grant list | R01 AI067727 / AI / NIAID NIH HHS / United States
R43 AI075692 / AI / NIAID NIH HHS / United States
D43TW007120 / TW / FIC NIH HHS / United States
K24AI068903 / AI / NIAID NIH HHS / United States
R01AI05759206 / AI / NIAID NIH HHS / United States
U19AI089681 / AI / NIAID NIH HHS / United States
R01 AI095916 / AI / NIAID NIH HHS / United States
R01RHLO86488 / PHS HHS / United States
AI075692 / AI / NIAID NIH HHS / United States
U19 AI089681 / AI / NIAID NIH HHS / United States
U19 AI089686 / AI / NIAID NIH HHS / United States
D43 TW007120 / TW / FIC NIH HHS / United States
1R01AI067727 / AI / NIAID NIH HHS / United States
K24 AI068903 / AI / NIAID NIH HHS / United States
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