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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/109044
Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study
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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.
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REQUENA, Pilar, ARÉVALO-HERRERA, Myriam, MENEGON, Michela, MARTÍNEZ ESPINOSA, Flor e., PADILLA, Norma, BOTTO MENEZES, Camila, MALHEIRO, Adriana, HANS, Dhiraj, CASTELLANOS, Maria eugenia, ROBINSON, Leanne j., SAMOL, Paula, KOCHAR, Swati, KOCHAR, Sanjay k., KOCHAR, Dhanpat k., DESAI, Meghna, SANZ, Sergi, QUINTÓ, Llorenç, MAYOR APARICIO, Alfredo gabriel, ROGERSON, Stephen john, MUELLER, Ivo, SEVERINI, Carlo, PORTILLO OBANDO, Hernando a. del, BARDAJÍ, Azucena, CHITNIS, Chetan e., MENÉNDEZ, Clara, DOBAÑO, Carlota. Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study. _Frontiers in Immunology_. 2017. Vol. 8, núm. 163. [consulta: 15 de gener de 2026]. ISSN: 1664-3224. [Disponible a: https://hdl.handle.net/2445/109044]