title: Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women.
abstract: P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy. Antibody responses against all antigens were detected in all populations, with PNG women presenting the highest levels overall. P. vivax infection at sample collection time was positively associated with antibody levels against PvLP1 (fold-increase: 1.60 at recruitment -first antenatal visit-) and PvLP2 (fold-increase: 1.63 at delivery), and P. falciparum co-infection was found to increase those responses (for PvLP1 at recruitment, fold-increase: 2.25). Levels of IgG against two VIR proteins at delivery were associated with higher birth weight (27 g increase per duplicating antibody levels, p<0.05). Peripheral blood mononuclear cells from PNG uninfected pregnant women had significantly higher antigen-specific IFN-γ TH1 responses (p=0.006) and secreted less pro-inflammatory cytokines TNF and IL-6 after PvLP2 stimulation than P. vivax-infected women (p<0.05). These data demonstrate that VIR antigens induce the natural acquisition of antibody and T cell memory responses that might be important in immunity to P. vivax during pregnancy in very diverse geographical settings.
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.|Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Pilar
authors.initials: P
authors.lastname: Requena
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Edmilson
authors.initials: E
authors.lastname: Rui
authors.affiliation: Centro de Estudios en Salud, Universidad del Valle de Guatemala, Guatemala City, Guatemala.
authors.forename: Norma
authors.initials: N
authors.lastname: Padilla
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.|Instituto Leônidas e Maria Deane (ILMD/Fiocruz Amazonia), Brazil.
authors.forename: Flor E
authors.initials: FE
authors.lastname: Martínez-Espinosa
authors.affiliation: Centro de Estudios en Salud, Universidad del Valle de Guatemala, Guatemala City, Guatemala.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Castellanos
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.|Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Bôtto-Menezes
authors.affiliation: Instituto de Ciências Biológicas. Universidade Federal do Amazonas, Manaus, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Malheiro
authors.affiliation: Caucaseco Scientific Research Center/Universidad del Valle, Cali, Colombia.
authors.forename: Myriam
authors.initials: M
authors.lastname: Arévalo-Herrera
authors.affiliation: Department of Medicine, Medical College, Bikaner, Rajasthan, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Kochar
authors.affiliation: Department of Medicine, Medical College, Bikaner, Rajasthan, India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Kochar
authors.affiliation: Department of Medicine, Medical College, Bikaner, Rajasthan, India.
authors.forename: Dhanpat K
authors.initials: DK
authors.lastname: Kochar
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Umbers
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Maria
authors.initials: M
authors.lastname: Ome-Kaius
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Regina
authors.initials: R
authors.lastname: Wangnapi
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Delhi, India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Hans
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Menegon
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mateo
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.affiliation: Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria, Malaria Branch, Atlanta, Georgia, United States of America.
authors.forename: Meghna
authors.initials: M
authors.lastname: Desai
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Delhi, India.
authors.forename: Chetan C
authors.initials: CC
authors.lastname: Chitnis
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Azucena
authors.initials: A
authors.lastname: Bardají
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.|Walter and Eliza Hall Institute, Parkville, Australia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rogerson
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Severini
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-Becerra
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.|ICREA, Barcelona, Spain.
authors.forename: Hernando
authors.initials: H
authors.lastname: Del Portillo
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Carlota
authors.identifier: http://orcid.org/0000-0002-6751-4060
authors.initials: C
authors.lastname: Dobaño
mesh_terms: D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D001724:Birth Weight; D001938:Brazil / Q000453:epidemiology; D015331:Cohort Studies; D060085:Coinfection / Q000276:immunology / Q000469:parasitology; D003105:Colombia / Q000453:epidemiology; D016207:Cytokines / Q000378:metabolism; D019353:Endemic Diseases; D005260:Female; D006166:Guatemala / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007156:Immunologic Memory; D007194:India / Q000453:epidemiology; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology; D016780:Malaria, Vivax / Q000453:epidemiology / Q000276:immunology*; D010219:Papua New Guinea / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D007371:Interferon-gamma