Genome-level determination of Plasmodium falciparum blood-stage targets of malarial clinical immunity in the Peruvian Amazon.
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.


RESULTS
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.
Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía.
Katherine J
KJ
Torres
Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía.
Carlos E
CE
Castrillon
Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Eli L
EL
Moss
Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía Division of Infectious Diseases, Department of Medicine, University of California-San Diego, La Jolla.
Mayuko
M
Saito
Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía Laboratorio Satelital, Universidad Peruana Cayetano Heredia, Iquitos, Perú
Roy
R
Tenorio
Antigen Discovery, Inc.
Douglas M
DM
Molina
Division of Infectious Diseases, Department of Medicine, University of California-Irvine.
Huw
H
Davies
Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Daniel E
DE
Neafsey
Division of Infectious Diseases, Department of Medicine, University of California-Irvine.
Philip
P
Felgner
Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía Institute de Medicina Tropical, Universidad Peruana Cayetano Heredia, Lima Division of Infectious Diseases, Department of Medicine, University of California-San Diego, La Jolla.
Joseph M
JM
Vinetz
Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía Institute de Medicina Tropical, Universidad Peruana Cayetano Heredia, Lima.
Dionicia
D
Gamboa
D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D002648:Child; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000097:blood / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000097:blood* / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins
geographic medicine; immunology; malaria; systems biology