Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women
Open accessAbstract
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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P.vivax infection by VIR antigens induces an IgG response.
“Another study demonstrated that P.vivax infection by VIR antigens induces an IgG response [95, 126].”
From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [126]
Requena et al. (2016) found that VIR antigens induce the natural acquisition of antibody and T-cell memory responses that may be critical for immunity against P.vivax during pregnancy in different geographic regions.
“Requena et al. (2016) found that VIR antigens induce the natural acquisition of antibody and T-cell memory responses that may be critical for immunity against P.vivax during pregnancy in different geographic regions [125].”
From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [125]
Requena et al. (2016) found that VIR antigens induce the natural acquisition of antibody and T-cell memory responses that may be critical for immunity against P.vivax during pregnancy in different geographic regions.
“Requena et al. (2016) found that VIR antigens induce the natural acquisition of antibody and T-cell memory responses that may be critical for immunity against P.vivax during pregnancy in different geographic regions [125].”
From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as Requena et al. (2016)
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- Authors
- Requena, P., Rui, E., Padilla, N., Martínez-Espinosa, F. E., Castellanos, M. E., Bôtto-Menezes, C., Malheiro, A., Arévalo-Herrera, M., Kochar, S., Kochar, S. K., Kochar, D. K., Umbers, A. J., Ome-Kaius, M., Wangnapi, R., Hans, D., Menegon, M., Mateo, F., Sanz, S., Desai, M., Mayor, A., Chitnis, C. C., Bardají, A., Mueller, I., Rogerson, S., Severini, C., Fernández-Becerra, C., Menéndez, C., del Portillo, H., & Dobaño, C.
- Affiliations
- Liverpool School of Tropical Medicine (GB)
- Barcelona Institute for Global Health (ES)
- Universidad del Valle de Guatemala (GT)
- Fundação de Medicina Tropical (BR)
- Universidade Federal do Amazonas (BR)
- The University of Melbourne (AU)
- Papua New Guinea Institute of Medical Research (PG)
- International Centre for Genetic Engineering and Biotechnology (IN)
- Istituto Superiore di Sanità (IT)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Dobaño, Carlota
- ORCID
- Venue
- PLOS Neglected Tropical Diseases
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-10-06
- Volume
- 10
- Issue
- 10
- Pages
- e0005009
- ISSN
- 1935-2727 (ISSN-L)
- 1935-2735
- PMC
- PMC5053494
- OpenAlex
- W2528788997
- Cited by
- 24
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 4 · 2017: 2
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/publicdomain/zero/1.0/ (vor)
- Locations
- PLoS neglected tropical diseases (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, public-domain)
- LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
- ResearchOnline - JCU (James Cook University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, public-domain)
- Funders
- Seventh Framework Programme (201588)
- Ministerio de Energia y competitividad (EUS2009-03560)
- Bill and Melinda Gates Foundation (46099)
- Ministerio de Economía y Competitividad (RYC-2008-02631)
- 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 › Parasitology › Vector-borne infectious diseases
- Keywords
- Plasmodium vivax, malaria in pregnancy, natural immunity, naturally acquired antibodies, T cell response, interferon-gamma, birth weight, cytokine production, malaria vaccine targets
- MeSH terms
- Adult, Antibodies, Protozoan, Antigens, Protozoan, Birth Weight, Brazil, Colombia, Female, Guatemala, Humans, Immunoglobulin G, Immunologic Memory, India, Interferon-gamma, Leukocytes, Mononuclear, Papua New Guinea, Plasmodium falciparum, Plasmodium vivax, Pregnancy, Pregnancy Complications, Infectious, Cohort Studies, Protozoan Proteins, Cytokines, Malaria, Falciparum, Malaria, Vivax, Th1 Cells, Endemic Diseases, Coinfection
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