Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women
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...
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2016
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pubmed-50534942016-10-27 Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women 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 Dobaño, Carlota Research Article 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. Public Library of Science 2016-10-06 /pmc/articles/PMC5053494/ /pubmed/27711158 http://dx.doi.org/10.1371/journal.pntd.0005009 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
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Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
building |
NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
author |
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 Dobaño, Carlota |
spellingShingle |
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 Dobaño, Carlota Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women |
author_facet |
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 Dobaño, Carlota |
author_sort |
Requena, Pilar |
title |
Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women |
title_short |
Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women |
title_full |
Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women |
title_fullStr |
Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women |
title_full_unstemmed |
Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women |
title_sort |
plasmodium vivax vir proteins are targets of naturally-acquired antibody and t cell immune responses to malaria in pregnant women |
description |
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. |
publisher |
Public Library of Science |
publishDate |
2016 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053494/ |
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1613675398325862400 |