Functional Antibodies against VAR2CSA in Nonpregnant Populations from Colombia Exposed to Plasmodium falciparum and Plasmodium vivax
Open accessAbstract
In pregnancy, parity-dependent immunity is observed in response to placental infection with Plasmodium falciparum . Antibodies recognize the surface antigen, VAR2CSA, expressed on infected red blood cells and inhibit cytoadherence to the placental tissue. In most settings of malaria endemicity, antibodies against VAR2CSA are predominantly observed in multigravid women and infrequently in men, children, and nulligravid women. However, in Colombia, we detected antibodies against multiple constructs of VAR2CSA among men and children with acute P. falciparum and Plasmodium vivax infection. The majority of men and children (>60%) had high levels of IgGs against three recombinant domains of VAR2CSA: DBL5ε, DBL3X, and ID1-ID2. Surprisingly, these antibodies were observed only in pregnant women, men, and children exposed either to P. falciparum or to P. vivax . Moreover, the anti-VAR2CSA antibodies are of high avidity and efficiently inhibit adherence of infected red blood cells to chondroitin sulfate A in vitro , suggesting that they are specific and functional. These unexpected results suggest that there may be genotypic or phenotypic differences in the parasites of this region or in the host response to either P. falciparum or P. vivax infection outside pregnancy. These findings may hold significant clinical relevance to the pathophysiology and outcome of malaria infections in this region.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Prior work, in conjunction with the data presented here, suggests that in this population and malaria transmission area, antibodies to the full-length VAR2CSA protein may be acquired outside of pregnancy.
“This prior work, in conjunction with the data presented here, suggests that in this population and malaria transmission area, antibodies to the full-length VAR2CSA protein may be acquired outside of pregnancy.”
From Clinical outcomes of submicroscopic infections and correlates of protection of VAR2CSA antibodies in a longitudinal study of pregnant women in Colombia (2018) · cites this paper as [30]
Pregnant women, men, and children who were infected with only P. vivax had antibodies that cross-reacted with the DBL5ε, DBL3X, and ID1-ID2 domains of VAR2CSA with similar frequencies.
“This is supported by our findings that pregnant women, men, and children who were infected with only P. vivax had antibodies that cross-reacted with the DBL5, DBL3X, and ID1-ID2 domains of VAR2CSA with similar frequencies (30).”
From Clinical outcomes of submicroscopic infections and correlates of protection of VAR2CSA antibodies in a longitudinal study of pregnant women in Colombia (2018) · cites this paper as [30]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Epidemiology and burden of malaria in pregnancy
Desai, M., ter Kuile, F. O., Nosten, F., McGready, R., Asamoa, K., Brabin, B., & Newman, R. D. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70021-x · Cited by 1,432 · see citing works
Adherence of <i>Plasmodium falciparum</i> to Chondroitin Sulfate A in the Human Placenta
Fried, M., & Duffy, P. E. (1996) · Science · doi:10.1126/science.272.5267.1502 · Cited by 1,108 · see citing works
Salanti, A., Staalsoe, T., Lavstsen, T., Jensen, A. T. R., Sowa, M. P. K., Arnot, D. E., Hviid, L., & Theander, T. G. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03570.x · Cited by 702 · see citing works
Plowe, C. V., DJIMDÉ, A. A., Bouaré, M., Doumbo, O. K., & Wellems, T. E. (1995) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1995.52.565 · Cited by 675 · see citing works
Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria
Salanti, A., Dahlbäck, M., Turner, L., Nielsen, M. A., Barfod, L., Magistrado, P., Jensen, A. T. R., Lavstsen, T., Ofori, M. F., Marsh, K., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041579 · Cited by 604 · see citing works
Leech, J., Barnwell, J., Miller, L., & Howard, R. J. (1984) · Journal of Experimental Medicine · doi:10.1084/jem.159.6.1567 · Cited by 422 · see citing works
Cheng, Q., Cloonan, N., Fischer, K., Thompson, J. K., Waine, G., Lanzer, M., & Saul, A. (1998) · Molecular and biochemical parasitology (Print) · doi:10.1016/s0166-6851(98)00144-3 · Cited by 292 · see citing works
Smith, J. D., Subramanian, G., Gamain, B., Baruch, D. I., & Miller, L. H. (2000) · Molecular and Biochemical Parasitology · doi:10.1016/s0166-6851(00)00279-6 · Cited by 276 · see citing works
Shokoples, S. E., Ndao, M., Kowalewska‐Grochowska, K., & Yanow, S. K. (2009) · Journal of Clinical Microbiology · doi:10.1128/jcm.01858-08 · Cited by 249 · see citing works
Self-citationWinter, G., Kawai, S., Haeggström, M., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041392 · Cited by 196 · see citing works
Richards, J. S., Stanisic, D. I., Fowkes, F. J. I., Tavul, L., Dabod, E., Thompson, J. K., Kumar, S., Chitnis, C. E., Narum, D. L., Michon, P., et al. (2010) · Clinical Infectious Diseases · doi:10.1086/656413 · Cited by 192 · see citing works
Malaria in pregnancy and the endemicity spectrum: what can we learn?
Nosten, F. H., Rogerson, S. J., Beeson, J. G., McGready, R. M., Mutabingwa, T. K., & Brabin, B. J. (2004) · Trends in Parasitology · doi:10.1016/j.pt.2004.06.007 · Cited by 184 · see citing works
High Level of<i>var2csa</i>Transcription by<i>Plasmodium falciparum</i>Isolated from the Placenta
Tuikue Ndam, N. G., Salanti, A., Bertin, G., Dahlbäck, M., Fievet, N., Turner, L., Gaye, A., Theander, T., & Deloron, P. (2005) · The Journal of Infectious Diseases · doi:10.1086/430933 · Cited by 179 · see citing works
Clausen, T. M., Christoffersen, S., Dahlbäck, M., Langkilde, A. E., Jensen, K. E., Resende, M., Agerbæk, M. Ø., Andersen, D., Berisha, B., Ditlev, S. B., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.348839 · Cited by 173 · see citing works
Epidemiology and control of malaria in Colombia
Padilla, J. C., Uribe, G. Á., Montoya, R. A., Narváez, P. E. C., & Valencia, S. H. (2011) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762011000900015 · Cited by 152 · see citing works
Gamain, B., Trimnell, A. R., Scheidig, C., Scherf, A., Miller, L. H., & Smith, J. D. (2005) · The Journal of Infectious Diseases · doi:10.1086/428137 · Cited by 145 · see citing works
Kaviratne, M., Khan, S. M., Jarra, W., & Preiser, P. R. (2002) · Eukaryotic Cell · doi:10.1128/ec.1.6.926-935.2002 · Cited by 133 · see citing works
Khunrae, P., Dahlbäck, M., Nielsen, M. A., Andersen, G., Ditlev, S. B., Resende, M., Pinto, V. V., Theander, T. G., Higgins, M. K., & Salanti, A. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.01.040 · Cited by 121 · see citing works
Multiple independent introductions of Plasmodium falciparum in South America
Yalcindag, E., Elguero, É., Arnathau, C., Durand, P., Akiana, J., Anderson, T. J. C., Aubouy, A., Balloux, F., Besnard, P., Bogreau, H., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119058109 · Cited by 116 · see citing works
Self-citationTheisen, M., Vuust, J., Gottschau, A., et al. (1995) · Clinical and Diagnostic Laboratory Immunology · doi:10.1128/cdli.2.1.30-34.1995 · Cited by 113 · see citing works
Dahlbäck, M., Rask, T. S., Andersen, P. H., Nielsen, M. A., Ndam, N. T., Resende, M., Turner, L., Deloron, P., Hviid, L., Lund, O., et al. (2006) · PLoS Pathogens · doi:10.1371/journal.ppat.0020124 · Cited by 98 · see citing works
Self-citationDynamics of Anti‐VAR2CSA Immunoglobulin G Response in a Cohort of Senegalese Pregnant Women
Tuikue Ndam, N. G., Salanti, A., Le‐Hesran, J. ‐., Cottrell, G., Fievet, N., Turner, L., Sow, S., Dangou, J. ‐., Theander, T., & Deloron, P. (2006) · The Journal of Infectious Diseases · doi:10.1086/500146 · Cited by 89 · see citing works
Barfod, L. K., Dalgaard, M. B., Pleman, S. T., Ofori, M. F., Pleass, R. J., & Hviid, L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103708108 · Cited by 84 · see citing works
Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA
Andersen, P., Nielsen, M. A., Resende, M., Rask, T. S., Dahlbäck, M., Theander, T., Lund, O., & Salanti, A. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.0040042 · Cited by 79 · see citing works
Disruption of Var2csa Gene Impairs Placental Malaria Associated Adhesion Phenotype
Viebig, N. K., Levin, E., Dechavanne, S., Rogerson, S. J., Gysin, J., Smith, J. D., Scherf, A., & Gamain, B. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000910 · Cited by 79 · see citing works
Chaiyaroj, S. C., Angkasekwinai, P., Buranakiti, A., Looareesuwan, S., Rogerson, S. J., & Brown, G. V. (1996) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1996.55.76 · Cited by 76 · see citing works
Naranjo-Díaz, N., Rosero-García, D., Rúa‐Uribe, G., et al. (2013) · Parasites & Vectors · doi:10.1186/1756-3305-6-61 · Cited by 72 · see citing works
Rasti, N., Namusoke, F., Chêne, A., Chen, Q., Staalsoe, T., Klinkert, M.-Q., Mirembe, F., Kironde, F., & Wahlgren, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601519103 · Cited by 69 · see citing works
Ndam, N. T., Fiévet, N., Bertin, G. I., Cottrell, G., Gaye, A., & Deloron, P. (2004) · The Journal of Infectious Diseases · doi:10.1086/425521 · Cited by 67 · see citing works
Self-citationBigey, P., Gnidehou, S., Doritchamou, J., Quiviger, M., Viwami, F., Couturier, A., Salanti, A., Nielsen, M. A., Scherman, D., Deloron, P., et al. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir499 · Cited by 63 · see citing works
Self-citationCharacterization of anti-var2CSA-PfEMP1 cytoadhesion inhibitory mouse monoclonal antibodies
Avril, M., Gamain, B., Lépolard, C., Viaud, N., Scherf, A., & Gysin, J. (2006) · Microbes and Infection · doi:10.1016/j.micinf.2006.09.005 · Cited by 61 · see citing works
The distinct proteome of placental malaria parasites
Fried, M., Hixson, K. K., Anderson, L., Ogata, Y., Mutabingwa, T. K., & Duffy, P. E. (2007) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2007.05.010 · Cited by 61 · see citing works
Oleinikov, A. V., Rossnagle, E., Francis, S., Mutabingwa, T. K., Fried, M., & Duffy, P. E. (2007) · The Journal of Infectious Diseases · doi:10.1086/518513 · Cited by 59 · see citing works
Campos, I. M., Uribe, M. L., Cuesta, C., Franco-Gallego, A., Carmona-Fonseca, J., & Maestre, A. (2011) · The American Society of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2011.10-0507 · Cited by 59 · see citing works
Self-citationArango, E. M., Samuel, R., Agudelo, O. M., Carmona-Fonseca, J., Maestre, A., & Yanow, S. K. (2013) · The American Society of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.12-0669 · Cited by 55 · see citing works
Self-citationBeeson, J. G., Ndungu, F. M., Persson, K. E. M., Chesson, J. M., Kelly, G., Uyoga, S. M., Hallamore, S. L., Williams, T. N., Reeder, J. C., Brown, G. V., et al. (2007) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2007.77.22 · Cited by 53 · see citing works
Haase, R. N., Megnekou, R., Lundquist, M., Ofori, M. F., Hviid, L., & Staalsøe, T. (2006) · Infection and Immunity · doi:10.1128/iai.74.5.3035-3038.2006 · Cited by 52 · see citing works
First-Trimester Plasmodium falciparum Infections Display a Typical “Placental” Phenotype
Doritchamou, J., Bertin, G. I., Moussiliou, A., Bigey, P., Viwami, F., Ezinmègnon, S., Fiévet, N., Massougbodji, A., Deloron, P., & Ndam, N. T. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis629 · Cited by 52 · see citing works
Self-citationHviid, L. (2004) · Parasite Immunology · doi:10.1111/j.0141-9838.2004.00733.x · Cited by 50 · see citing works
Magistrado, P. A., Minja, D., Doritchamou, J., Tuikue Ndam, N., John, D., Schmiegelow, C., Massougbodji, A., Dahlbäck, M., Ditlev, S. B., Pinto, V. V., et al. (2011) · Vaccine · doi:10.1016/j.vaccine.2010.10.080 · Cited by 49 · see citing works
Self-citationResende, M., Ditlev, S. B., Nielsen, M. A., Bodevin, S., Bruun, S., Pinto, V. V., Clausen, H., Turner, L., Theander, T. G., Salanti, A., et al. (2009) · International Journal for Parasitology · doi:10.1016/j.ijpara.2009.02.022 · Cited by 48 · see citing works
Oleinikov, A. V., Voronkova, V. V., Frye, I. T., Amos, E., Morrison, R., Fried, M., & Duffy, P. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031011 · Cited by 41 · see citing works
Malaria transmission in the lagoon area of Cotonou, Benin.
Akogbeto, M. C., Modiano, D., & Bosman, A. (1992) · PubMed · Cited by 32 · see citing works
Zakeri, S., Babaeekhou, L., Mehrizi, A. A., Abbasi, M. A., & Djadid, N. D. (2011) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2011.11-0001 · Cited by 30 · see citing works
Gnidehou, S., Jessen, L. E., Gangnard, S., Ermont, C., Triqui, C., Quiviger, M., Guitard, J., Lund, O., Deloron, P., & Ndam, N. T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013105 · Cited by 18 · see citing works
Self-citationPlasmodium falciparum population dynamics in a cohort of pregnant women in Senegal
Guitard, J., Andersen, P., Ermont, C., Gnidehou, S., Fiévet, N., Lund, O., Deloron, P., & Ndam, N. T. (2010) · Malaria Journal · doi:10.1186/1475-2875-9-165 · Cited by 16 · see citing works
Self-citationAnalysis of CSA-Binding Parasites and Antiadhesion Antibodies
Fried, M., & Duffy, P. E. (2003) · Humana Press eBooks · doi:10.1385/1-59259-271-6:555 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Designing a VAR2CSA-based vaccine to prevent placental malaria
Fried, M., & Duffy, P. E. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.10.011 · Cited by 86 · see citing works
“[41] reported that in Colombia, children, men and pregnant women exposed to malaria have similar antibody levels to ID1– DBL2–ID2a, DBL3 and DBL5 domains.”
BackgroundGavina, K., Gnidehou, S., Arango, E., Hamel-Martineau, C., Mitran, C., Agudelo, O., Lopez, C., Karidio, A., Banman, S., Carmona-Fonseca, J., et al. (2018) · Infection and Immunity · doi:10.1128/iai.00797-17 · Cited by 26 · see citing works
Self-citationLopez-Perez, M., Larsen, M. D., Bayarri-Olmos, R., Ampomah, P., Stevenson, L., Arévalo-Herrera, M., Herrera, S., & Hviid, L. (2018) · Infection and Immunity · doi:10.1128/iai.00136-18 · Cited by 24 · see citing works
Iyamu, U., Vinals, D. F., Tornyigah, B., Arango, E., Bhat, R., Adra, T. R., Grewal, S., Martin, K., Maestre, A., Overduin, M., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1202276 · Cited by 7 · see citing works
Self-citation
- Authors
- Gnidehou, S., Doritchamou, J., Arango, E. M., Cabrera, A., Arroyo, M. I., Kain, K. C., Ndam, N. T., Maestre, A., & Yanow, S. K.
- Affiliations
- School of Public Health, University of Alberta, Edmonton, Canada
- Sorbonne Paris Cité (FR)
- Universidad de Antioquia (CO)
- University Health Network (CA)
- Grupo Salud y Comunidad, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
- University of Alberta (CA)
- ORCID
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2014-06
- Volume
- 82
- Issue
- 6
- Pages
- 2565-2573
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC4019168
- OpenAlex
- W2003942367
- Cited by
- 34
- References
- 47
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 4
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository University of Antioquia (University of Antioquia) (submittedVersion, cc-by)
- Funders
- Canadian Institutes of Health Research (125971_1, 13721, 115440, 115160_1)
- 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
- VAR2CSA, Plasmodium falciparum, Plasmodium vivax, placental malaria, chondroitin sulfate A, cytoadherence, antibody avidity, malaria immunity, Colombia
- MeSH terms
- Adolescent, Adult, Aged, Antibodies, Protozoan, Antibody Affinity, Antigens, Protozoan, Child, Child, Preschool, Colombia, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoglobulin G, Male, Middle Aged, Plasmodium falciparum, Plasmodium vivax, Pregnancy, Malaria, Falciparum, Malaria, Vivax, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
