Cited by 13Malaria Research and ControlBlood groups and transfusionReproductive System and Pregnancy

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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Requena, Pilar, Arévalo-Herrera, Myriam, Menegon, Michela, Martínez-Espinosa, Flor E., Padilla, Norma, Bôtto-Menezes, Camila, Malheiro, Adriana, Hans, Dhiraj +18 more·2017·Frontiers in Immunology

Abstract

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 P. 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 P. falciparum (Pf) antigens (ii) the capacity of anti-PvDBP antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to 2 Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG). There were significant intra-species and inter-species 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 co-infection 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 they are markers of malaria exposure. PBMCs from Pv-infected women presented fewer CD8+IFN-γ+ 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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  • Early detection of Plasmodium parasites can be performed through various methods, such as TBS, RDTs, and PCR.

    “Early detection of Plasmodium parasites can be performed through various methods, such as TBS, RDTs, and PCR [127, 137].”

    From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [127]

    The Materials and Methods (Study Design and Population; Plasmodium spp. Detection by PCR) describe detecting infection with thick blood smears, PCR, and—in symptomatic women in Papua New Guinea—rapid diagnostic tests. The paper supports these as detection methods but does not establish that all three enable early detection. (LLM, conf=0.84)

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  1. [27]Arévalo-Herrera M Chitnis C Herrera S. Current status of Plasmodium vivax vaccine. Hum Vaccin (2010) 6: 124– 32. 20009526

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Authors
Requena, P., Arévalo-Herrera, M., Menegon, M., Martínez-Espinosa, F. E., Padilla, N., Bôtto-Menezes, C., Malheiro, A., Hans, D., Castellanos, M. E., Robinson, L., Samol, P., Kochar, S., Kochar, S. K., Kochar, D. K., Desai, M., Sanz, S., Quintó, L., Mayor, A., Rogerson, S., Mueller, I., Severini, C., del Portillo, H. A., Bardají, A., Chitnis, C. C., Menéndez, C., & Dobaño, C.
Affiliations
  • Hospital Clínic de Barcelona (ES)
  • Istituto Superiore di Sanità (IT)
  • Fundação de Medicina Tropical (BR)
  • Universidad del Valle de Guatemala (GT)
  • Universidade do Estado do Amazonas (BR)
  • Universidade Federal do Amazonas (BR)
  • International Centre for Genetic Engineering and Biotechnology (IN)
  • Burnet Institute (AU)
  • Papua New Guinea Institute of Medical Research (PG)
  • Centers for Disease Control and Prevention (US)
  • The University of Melbourne (AU)
Corresponding author
  • Requena, Pilar
  • Dobaño, Carlota
Venue
Frontiers in Immunology
Published
2017-02-17
Volume
8
Pages
163-163
ISSN
1664-3224 (ISSN-L)
OpenAlex
W2588422178
Cited by
13
References
72
Citations by year
2026: 1 · 2025: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 1
FWCI
1.54
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, cc-by)
  • ResearchOnline at James Cook University (James Cook University) (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by)
  • Greater South Information System
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
Plasmodium vivax, Duffy binding protein, pregnancy, birth weight, malaria vaccine targets, naturally acquired immunity, submicroscopic malaria infection, cytokine production

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