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Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women

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Requena, Pilar, Rui, Edmilson, Padilla, Norma, Martínez-Espinosa, Flor E., Castellanos, Maria Eugenia, Bôtto-Menezes, Camila, Malheiro, Adriana, Arévalo-Herrera, Myriam, Kochar, Swati, Kochar, Sanjay K., Kochar, Dhanpat K., Umbers, Alexandra J., Ome-Kaius, Maria, Wangnapi, Regina, Hans, Dhiraj, Menegon, Michela, Mateo, Francesca, Sanz, Sergi, Desai, Meghna, Mayor, Alfredo, Chitnis, Chetan C., Bardají, Azucena, Mueller, Ivo, Rogerson, Stephen, Severini, Carlo, Fernández-Becerra, Carmen, Menéndez, Clara, del Portillo, Hernando and Dobaño, Carlota (2016) 'Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women'. PLoS Neglected Tropical Diseases, Vol 10, Issue 10, e0005009.

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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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WQ Obstetrics > Pregnancy Complications > WQ 256 Infectious diseases
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pntd.0005009
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 07 Oct 2016 14:13
Last Modified: 06 Feb 2018 13:13
URI: https://archive.lstmed.ac.uk/id/eprint/6246

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