title: Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection.
abstract: Large scale antibody responses in Plasmodium vivax malaria remains unexplored in the endemic setting. Protein microarray analysis of asexual-stage P. vivax was used to identify antigens recognized in sera from residents of hypoendemic Peruvian Amazon. Over 24 months, of 106 participants, 91 had two symptomatic P. vivax malaria episodes, 11 had three episodes, 3 had four episodes, and 1 had five episodes. Plasmodium vivax relapse was distinguished from reinfection by a merozoite surface protein-3α restriction fragment length polymorphism polymerase chain reaction (MSP3α PCR-RFLP) assay. Notably, P. vivax reinfection subjects did not have higher reactivity to the entire set of recognized P. vivax blood-stage antigens than relapse subjects, regardless of the number of malaria episodes. The most highly recognized P. vivax proteins were MSP 4, 7, 8, and 10 (PVX_003775, PVX_082650, PVX_097625, and PVX_114145); sexual-stage antigen s16 (PVX_000930); early transcribed membrane protein (PVX_090230); tryptophan-rich antigen (Pv-fam-a) (PVX_092995); apical merozoite antigen 1 (PVX_092275); and proteins of unknown function (PVX_081830, PVX_117680, PVX_118705, PVX_121935, PVX_097730, PVX_110935, PVX_115450, and PVX_082475). Genes encoding reactive proteins exhibited a significant enrichment of non-synonymous nucleotide variation, an observation suggesting immune selection. These data identify candidates for seroepidemiological tools to support malaria elimination efforts in P. vivax-endemic regions.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Raul
authors.initials: R
authors.lastname: Chuquiyauri
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Molina
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Eli L
authors.initials: EL
authors.lastname: Moss
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Gardner
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Brouwer
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Torres
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Llanos-Cuentas
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Neafsey
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Philip
authors.initials: P
authors.lastname: Felgner
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California San Diego, La Jolla, California; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú; Antigen Discovery Inc., Irvine, California; Malaria Research Group, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; Seattle Biomed, Seattle, Washington; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland jvinetz@ucsd.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Vinetz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000913:Antibodies, Protozoan / Q000276:immunology*; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D016780:Malaria, Vivax / Q000276:immunology*; D008297:Male; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040081:Protein Array Analysis; D012008:Recurrence; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan