Katherine J Torres1, Carlos E Castrillon1, Eli L Moss2, Mayuko Saito3, Roy Tenorio4, Douglas M Molina5, Huw Davies6, Daniel E Neafsey2, Philip Felgner6, Joseph M Vinetz7, Dionicia Gamboa8. 1. Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía. 2. Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts. 3. 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. 4. Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía Laboratorio Satelital, Universidad Peruana Cayetano Heredia, Iquitos, Perú 5. Antigen Discovery, Inc. 6. Division of Infectious Diseases, Department of Medicine, University of California-Irvine. 7. 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. 8. Laboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía Institute de Medicina Tropical, Universidad Peruana Cayetano Heredia, Lima.
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.
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.
Authors: Fabiana P Alves; Rui R Durlacher; Maria J Menezes; Henrique Krieger; Luiz H Pereira Silva; Erney P Camargo Journal: Am J Trop Med Hyg Date: 2002-06 Impact factor: 2.345
Authors: D L Doolan; J C Aguiar; W R Weiss; A Sette; P L Felgner; D P Regis; P Quinones-Casas; J R Yates; P L Blair; T L Richie; S L Hoffman; D J Carucci Journal: J Exp Biol Date: 2003-11 Impact factor: 3.312
Authors: Baback Roshanravan; Elina Kari; Robert H Gilman; Lilia Cabrera; Ellen Lee; John Metcalfe; Maritza Calderon; Andres G Lescano; Sonia H Montenegro; Carlos Calampa; Joseph M Vinetz Journal: Am J Trop Med Hyg Date: 2003-07 Impact factor: 2.345
Authors: M R van Dijk; C J Janse; J Thompson; A P Waters; J A Braks; H J Dodemont; H G Stunnenberg; G J van Gemert; R W Sauerwein; W Eling Journal: Cell Date: 2001-01-12 Impact factor: 41.582
Authors: Yossef Alnasser; Cusi Ferradas; Taryn Clark; Maritza Calderon; Alejandro Gurbillon; Dionicia Gamboa; Uri S McKakpo; Isabella A Quakyi; Kwabena M Bosompem; David J Sullivan; Joseph M Vinetz; Robert H Gilman Journal: PLoS Negl Trop Dis Date: 2016-10-05
Authors: Abdirahman Abdi; Lu Yu; David Goulding; Martin K Rono; Philip Bejon; Jyoti Choudhary; Julian Rayner Journal: Wellcome Open Res Date: 2017-11-22
Authors: Gabriel Carrasco-Escobar; Dionicia Gamboa; Marcia C Castro; Shrikant I Bangdiwala; Hugo Rodriguez; Juan Contreras-Mancilla; Freddy Alava; Niko Speybroeck; Andres G Lescano; Joseph M Vinetz; Angel Rosas-Aguirre; Alejandro Llanos-Cuentas Journal: Sci Rep Date: 2017-08-14 Impact factor: 4.379
Authors: Sara E White; Steven A Harvey; Graciela Meza; Alejandro Llanos; Mitchel Guzman; Dionicia Gamboa; Joseph M Vinetz Journal: Malar J Date: 2018-04-27 Impact factor: 2.979
Authors: Christopher L King; D Huw Davies; Phil Felgner; Elizabeth Baum; Aarti Jain; Arlo Randall; Kevin Tetteh; Christopher J Drakeley; Bryan Greenhouse Journal: Am J Trop Med Hyg Date: 2015-08-10 Impact factor: 2.345