Autor/a:
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Requena, Pilar; Rui, Edmilson; Padilla, Norma; Martínez Espinosa, Flor E.; Castellanos, Maria Eugenia; Botto Menezes, Camila; Malheiro, Adriana; Arévalo-Herrera, Myriam; Kochar, Swati; Kochar, Sanjay K.; Kochar, Dhanpat K.; Umbers, Alexandra J.; Ome-Kaius, Maria; Wangnapi, Regina A.; Hans, Dhiraj; Menegon, Michela; Mateo, Francesca; Sanz, Sergi; Desai, Meghna; Mayor Aparicio, Alfredo Gabriel; Chitnis, Chetan E.; Bardají, Azucena; Mueller, Ivo; Rogerson, Stephen John; Severini, Carlo; Fernández Becerra, Carmen; Menéndez, Clara; Portillo Obando, Hernando A. del; Dobaño, Carlota, 1969-
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Abstract:
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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-gamma 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. |