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PLoS Negl Trop Dis. 2016 Oct 6;10(10):e0005009. doi: 10.1371/journal.pntd.0005009. eCollection 2016 Oct.

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

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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.
Centro de Estudios en Salud, Universidad del Valle de Guatemala, Guatemala City, Guatemala.
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
Instituto Leônidas e Maria Deane (ILMD/Fiocruz Amazonia), Brazil.
Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
Instituto de Ciências Biológicas. Universidade Federal do Amazonas, Manaus, Brazil.
Caucaseco Scientific Research Center/Universidad del Valle, Cali, Colombia.
Department of Medicine, Medical College, Bikaner, Rajasthan, India.
Department of Medicine, University of Melbourne, Melbourne, Australia.
Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
International Center for Genetic Engineering and Biotechnology, Delhi, India.
Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria, Malaria Branch, Atlanta, Georgia, United States of America.
Walter and Eliza Hall Institute, Parkville, Australia.
ICREA, Barcelona, Spain.


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.

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