Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens

Background Pregnant women exposed to Plasmodium falciparum generate antibodies against VAR2CSA, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. There is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to ide...

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Autores: Fonseca, Ana Maria, Quintó, Llorenç, Jiménez, Alfons, González, Raquel, Bardají, Azucena, Maculuve, Sónia Amós, Dobaño, Carlota, 1969-, Rupérez, María, Vala, Anifa, Aponte, John J., Sevene, Esperança Júlia Pires, Macete, Eusebio Víctor, Menéndez, Clara, Mayor Aparicio, Alfredo Gabriel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/114196
Acceso en línea:https://hdl.handle.net/2445/114196
Access Level:acceso abierto
Palabra clave:Plasmodium falciparum
Embarassades
Immunoglobulines
Pregnant women
Immunoglobulins
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spelling Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigensFonseca, Ana MariaQuintó, LlorençJiménez, AlfonsGonzález, RaquelBardají, AzucenaMaculuve, Sónia AmósDobaño, Carlota, 1969-Rupérez, MaríaVala, AnifaAponte, John J.Sevene, Esperança Júlia PiresMacete, Eusebio VíctorMenéndez, ClaraMayor Aparicio, Alfredo GabrielPlasmodium falciparumEmbarassadesImmunoglobulinesPlasmodium falciparumPregnant womenImmunoglobulinsBackground Pregnant women exposed to Plasmodium falciparum generate antibodies against VAR2CSA, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. There is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to identify immune correlates of protection and exposure. Here we aimed at developing a multiplex-immunoassay to detect antibodies against VAR2CSA antigens. Methods and findings We constructed two multiplex-bead arrays, one composed of 3 VAR2CSA recombinant-domains (DBL3X, DBL5Ɛ and DBL6Ɛ) and another composed of 46 new peptides covering VAR2CSA conserved and semi-conserved regions. IgG reactivity was similar in multiplexed and singleplexed determinations (Pearson correlation, protein array: R2 = 0.99 and peptide array: R2 = 0.87). IgG recognition of 25 out of 46 peptides and all recombinant-domains was higher in pregnant Mozambican women (n = 106) than in Mozambican men (n = 102) and Spanish individuals (n = 101; p<0.05). Agreement of IgG levels detected in cryopreserved plasma and in elutions from dried blood spots was good after exclusion of inappropriate filter papers. Under heterogeneous levels of exposure to malaria, similar seropositivity cutoffs were obtained using finite mixture models applied to antibodies measured on pregnant Mozambican women and average of antibodies measured on pregnant Spanish women never exposed to malaria. The application of the multiplex-bead array developed here, allowed the assessment of higher IgG levels and seroprevalences against VAR2CSA-derived antigens in women pregnant during 2003–2005 than during 2010–2012, in accordance with the levels of malaria transmission reported for these years in Mozambique. Conclusions The multiplex bead-based immunoassay to detect antibodies against selected 25 VAR2CSA new-peptides and recombinant-domains was successfully implemented. Analysis of field samples showed that responses were specific among pregnant women and dependent on the level of exposure to malaria. This platform provides a high-throughput approach to investigating correlates of protection and identifying serological markers of exposure for malaria in pregnancy.Public Library of Science (PLoS)2017201720172017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion20 p.application/pdfhttps://hdl.handle.net/2445/114196Articles publicats en revistes (ISGlobal)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0181150PLoS One, 2017, vol. 12, num. 7, 20 p.https://doi.org/10.1371/journal.pone.0181150cc by (c) Fonseca, Ana Maria et al., 2017http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1141962026-05-29T05:05:01Z
dc.title.none.fl_str_mv Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
title Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
spellingShingle Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
Fonseca, Ana Maria
Plasmodium falciparum
Embarassades
Immunoglobulines
Plasmodium falciparum
Pregnant women
Immunoglobulins
title_short Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
title_full Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
title_fullStr Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
title_full_unstemmed Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
title_sort Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens
dc.creator.none.fl_str_mv Fonseca, Ana Maria
Quintó, Llorenç
Jiménez, Alfons
González, Raquel
Bardají, Azucena
Maculuve, Sónia Amós
Dobaño, Carlota, 1969-
Rupérez, María
Vala, Anifa
Aponte, John J.
Sevene, Esperança Júlia Pires
Macete, Eusebio Víctor
Menéndez, Clara
Mayor Aparicio, Alfredo Gabriel
author Fonseca, Ana Maria
author_facet Fonseca, Ana Maria
Quintó, Llorenç
Jiménez, Alfons
González, Raquel
Bardají, Azucena
Maculuve, Sónia Amós
Dobaño, Carlota, 1969-
Rupérez, María
Vala, Anifa
Aponte, John J.
Sevene, Esperança Júlia Pires
Macete, Eusebio Víctor
Menéndez, Clara
Mayor Aparicio, Alfredo Gabriel
author_role author
author2 Quintó, Llorenç
Jiménez, Alfons
González, Raquel
Bardají, Azucena
Maculuve, Sónia Amós
Dobaño, Carlota, 1969-
Rupérez, María
Vala, Anifa
Aponte, John J.
Sevene, Esperança Júlia Pires
Macete, Eusebio Víctor
Menéndez, Clara
Mayor Aparicio, Alfredo Gabriel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Plasmodium falciparum
Embarassades
Immunoglobulines
Plasmodium falciparum
Pregnant women
Immunoglobulins
topic Plasmodium falciparum
Embarassades
Immunoglobulines
Plasmodium falciparum
Pregnant women
Immunoglobulins
description Background Pregnant women exposed to Plasmodium falciparum generate antibodies against VAR2CSA, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. There is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to identify immune correlates of protection and exposure. Here we aimed at developing a multiplex-immunoassay to detect antibodies against VAR2CSA antigens. Methods and findings We constructed two multiplex-bead arrays, one composed of 3 VAR2CSA recombinant-domains (DBL3X, DBL5Ɛ and DBL6Ɛ) and another composed of 46 new peptides covering VAR2CSA conserved and semi-conserved regions. IgG reactivity was similar in multiplexed and singleplexed determinations (Pearson correlation, protein array: R2 = 0.99 and peptide array: R2 = 0.87). IgG recognition of 25 out of 46 peptides and all recombinant-domains was higher in pregnant Mozambican women (n = 106) than in Mozambican men (n = 102) and Spanish individuals (n = 101; p<0.05). Agreement of IgG levels detected in cryopreserved plasma and in elutions from dried blood spots was good after exclusion of inappropriate filter papers. Under heterogeneous levels of exposure to malaria, similar seropositivity cutoffs were obtained using finite mixture models applied to antibodies measured on pregnant Mozambican women and average of antibodies measured on pregnant Spanish women never exposed to malaria. The application of the multiplex-bead array developed here, allowed the assessment of higher IgG levels and seroprevalences against VAR2CSA-derived antigens in women pregnant during 2003–2005 than during 2010–2012, in accordance with the levels of malaria transmission reported for these years in Mozambique. Conclusions The multiplex bead-based immunoassay to detect antibodies against selected 25 VAR2CSA new-peptides and recombinant-domains was successfully implemented. Analysis of field samples showed that responses were specific among pregnant women and dependent on the level of exposure to malaria. This platform provides a high-throughput approach to investigating correlates of protection and identifying serological markers of exposure for malaria in pregnancy.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/114196
url https://hdl.handle.net/2445/114196
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0181150
PLoS One, 2017, vol. 12, num. 7, 20 p.
https://doi.org/10.1371/journal.pone.0181150
dc.rights.none.fl_str_mv cc by (c) Fonseca, Ana Maria et al., 2017
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Fonseca, Ana Maria et al., 2017
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 20 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (ISGlobal)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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