Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study
| Autor: | Camila Bôtto-Menezes, Llorenç Quintó, Pilar Requena, Sanjay K. Kochar, Clara Menéndez, Michela Menegon, Stephen J. Rogerson, Leanne J. Robinson, Paula Samol, Swati Kochar, Carlota Dobaño, Adriana Malheiro, Flor Ernestina Martinez-Espinosa, Dhanpat K. Kochar, Alfredo Mayor, Sergi Sanz, Maria Eugenia Castellanos, Ivo Mueller, Myriam Arévalo-Herrera, Dhiraj Hans, Carlo Severini, Hernando A. del Portillo, Norma Padilla, Chetan C. Chitnis, Meghna Desai, Azucena Bardají |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
030231 tropical medicine Population Plasmodium vivax Immunology Malària PvDBP 03 medical and health sciences Embarassades 0302 clinical medicine Immune system falciparum Antigen Immunity parasitic diseases medicine Immunology and Allergy antibodies education education.field_of_study biology Pregnant women T cell biology.organism_classification medicine.disease Virology immunity malaria in pregnancy cytokines 3. Good health Malaria vivax Circumsporozoite protein 030104 developmental biology biology.protein Antibody |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2017.00163 |
| Popis: | A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events of Plasmodium infection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119 versus PfAMA1, Spearman's rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood mononuclear cells from Pv-infected women presented fewer CD8+IFN-gamma+ T cells and secreted more G-CSF and IL-4 independently of the stimulus used in vitro. Functional anti-PvDBP levels at recruitment had a positive association with birth weight (difference per doubling antibody levels: 45 g, p-value: 0.046). Thus, naturally acquired binding-inhibitory antibodies to PvDBP might confer protection against poor outcomes of Pv malaria in pregnancy. |
| Databáze: | OpenAIRE |
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