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

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

Requena P, Rui e, Padilla N, Martínez-Espinosa FE, Castellanos ME, BÔtto-Menezes C, Malheiro A, Arévalo-Herrera M, Kochar S, Kochar SK, Kochar DK, Umbers AJ, Ome-Kaius M, Wangnapi R, Hans D, Menegon M, Mateo F, Sanz S, Desai M, Mayor A, Chitnis CC, Bardaji A, Mueller I, Rogerson S, Severini C, Fernández-Becerra C, menéndez C, del Portillo H, Dobaño C.. Plasmodium vivax VIR Proteins are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women. PLoS Negl Trop Dis, 10(10): e0005009, 2016

doi:10.1371/journal.pntd.0005009.

 

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Description

Pvivax 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 Pvivax 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. Pvivax 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 Pfalciparum 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 Pvivax-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 Pvivax during pregnancy in very diverse geographical settings.

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