RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study

Dobaño, Carlota, 1969-; Ubillos, Itziar; Jairoce, Chenjerai Tobias Sixpence; Gyan, Ben; Vidal, Marta; Jiménez, Alfons; Santano, Rebeca; Dosoo, David; Nhabomba, Augusto J.; Ayestaran, Aintzane; Aguilar, Ruth; Williams, Nana Aba; Díez-Padrisa, Núria; Lanar, David; Chauhan, Virander; Chitnis, Chetan; Dutta, Sheetij; Gaur, Deepak; Angov, Evelina; Asante, Kwaku Poku; Owusu-Agyei, Seth; Valim, Clarissa; Gamain, Benoit; Coppel, Ross L.; Cavanagh, David; Beeson, James G.; Campo, Joseph J.; Moncunill Piñas, Gemma

RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study

Background: Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized th...

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Autores:	Dobaño, Carlota, 1969-, Ubillos, Itziar, Jairoce, Chenjerai Tobias Sixpence, Gyan, Ben, Vidal, Marta, Jiménez, Alfons, Santano, Rebeca, Dosoo, David, Nhabomba, Augusto J., Ayestaran, Aintzane, Aguilar, Ruth, Williams, Nana Aba, Díez-Padrisa, Núria, Lanar, David, Chauhan, Virander, Chitnis, Chetan, Dutta, Sheetij, Gaur, Deepak, Angov, Evelina, Asante, Kwaku Poku, Owusu-Agyei, Seth, Valim, Clarissa, Gamain, Benoit, Coppel, Ross L., Cavanagh, David, Beeson, James G., Campo, Joseph J., Moncunill Piñas, Gemma
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2019
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:2445/139548
Acceso en línea:	https://hdl.handle.net/2445/139548
Access Level:	acceso abierto
Palabra clave:	Malària Plasmodium falciparum Infants Àfrica Malaria Children Africa

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spelling	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control studyDobaño, Carlota, 1969-Ubillos, ItziarJairoce, Chenjerai Tobias SixpenceGyan, BenVidal, MartaJiménez, AlfonsSantano, RebecaDosoo, DavidNhabomba, Augusto J.Ayestaran, AintzaneAguilar, RuthWilliams, Nana AbaDíez-Padrisa, NúriaLanar, DavidChauhan, ViranderChitnis, ChetanDutta, SheetijGaur, DeepakAngov, EvelinaAsante, Kwaku PokuOwusu-Agyei, SethValim, ClarissaGamain, BenoitCoppel, Ross L.Cavanagh, DavidBeeson, James G.Campo, Joseph J.Moncunill Piñas, GemmaMalàriaPlasmodium falciparumInfantsÀfricaMalariaChildrenAfricaBackground: Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized that RTS,S/A01E immunization affects acquisition of antibodies to Plasmodium falciparum antigens not included in the vaccine and that such responses have an impact on overall malaria protective immunity. Methods: We evaluated IgM and IgG responses to 38 P. falciparum proteins putatively involved in naturally acquired immunity to malaria in 195 young children participating in a case-control study nested within the African phase 3 clinical trial of RTS,S/AS01E (MAL055 NCT00866619) in two sites of different transmission intensity (Kintampo high and Manhiça moderate/low). We measured antibody levels by quantitative suspension array technology and applied regression models, multimarker analysis, and machine learning techniques to analyze factors affecting their levels and correlates of protection. Results: RTS,S/AS01E immunization decreased antibody responses to parasite antigens considered as markers of exposure (MSP142, AMA1) and levels correlated with risk of clinical malaria over 1-year follow-up. In addition, we show for the first time that RTS,S vaccination increased IgG levels to a specific group of pre-erythrocytic and blood-stage antigens (MSP5, MSP1 block 2, RH4.2, EBA140, and SSP2/TRAP) which levels correlated with protection against clinical malaria (odds ratio [95% confidence interval] 0.53 [0.3–0.93], p = 0.03, for MSP1; 0.52 [0.26–0.98], p = 0.05, for SSP2) in multivariable logistic regression analyses. Conclusions: Increased antibody responses to specific P. falciparum antigens in subjects immunized with this partially efficacious vaccine upon natural infection may contribute to overall protective immunity against malaria. Inclusion of such antigens in multivalent constructs could result in more efficacious second-generation multistage vaccines.BioMed Central2019201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion19 p.application/pdfhttps://hdl.handle.net/2445/139548Articles 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: http://dx.doi.org/10.1186/s12916-019-1378-6BMC Medicine, 2019, vol. 17http://dx.doi.org/10.1186/s12916-019-1378-6cc by (c) Dobaño et al., 2019http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1395482026-05-29T05:05:01Z
dc.title.none.fl_str_mv	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
title	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
spellingShingle	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study Dobaño, Carlota, 1969- Malària Plasmodium falciparum Infants Àfrica Malaria Children Africa
title_short	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
title_full	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
title_fullStr	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
title_full_unstemmed	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
title_sort	RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
dc.creator.none.fl_str_mv	Dobaño, Carlota, 1969- Ubillos, Itziar Jairoce, Chenjerai Tobias Sixpence Gyan, Ben Vidal, Marta Jiménez, Alfons Santano, Rebeca Dosoo, David Nhabomba, Augusto J. Ayestaran, Aintzane Aguilar, Ruth Williams, Nana Aba Díez-Padrisa, Núria Lanar, David Chauhan, Virander Chitnis, Chetan Dutta, Sheetij Gaur, Deepak Angov, Evelina Asante, Kwaku Poku Owusu-Agyei, Seth Valim, Clarissa Gamain, Benoit Coppel, Ross L. Cavanagh, David Beeson, James G. Campo, Joseph J. Moncunill Piñas, Gemma
author	Dobaño, Carlota, 1969-
author_facet	Dobaño, Carlota, 1969- Ubillos, Itziar Jairoce, Chenjerai Tobias Sixpence Gyan, Ben Vidal, Marta Jiménez, Alfons Santano, Rebeca Dosoo, David Nhabomba, Augusto J. Ayestaran, Aintzane Aguilar, Ruth Williams, Nana Aba Díez-Padrisa, Núria Lanar, David Chauhan, Virander Chitnis, Chetan Dutta, Sheetij Gaur, Deepak Angov, Evelina Asante, Kwaku Poku Owusu-Agyei, Seth Valim, Clarissa Gamain, Benoit Coppel, Ross L. Cavanagh, David Beeson, James G. Campo, Joseph J. Moncunill Piñas, Gemma
author_role	author
author2	Ubillos, Itziar Jairoce, Chenjerai Tobias Sixpence Gyan, Ben Vidal, Marta Jiménez, Alfons Santano, Rebeca Dosoo, David Nhabomba, Augusto J. Ayestaran, Aintzane Aguilar, Ruth Williams, Nana Aba Díez-Padrisa, Núria Lanar, David Chauhan, Virander Chitnis, Chetan Dutta, Sheetij Gaur, Deepak Angov, Evelina Asante, Kwaku Poku Owusu-Agyei, Seth Valim, Clarissa Gamain, Benoit Coppel, Ross L. Cavanagh, David Beeson, James G. Campo, Joseph J. Moncunill Piñas, Gemma
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Malària Plasmodium falciparum Infants Àfrica Malaria Children Africa
topic	Malària Plasmodium falciparum Infants Àfrica Malaria Children Africa
description	Background: Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized that RTS,S/A01E immunization affects acquisition of antibodies to Plasmodium falciparum antigens not included in the vaccine and that such responses have an impact on overall malaria protective immunity. Methods: We evaluated IgM and IgG responses to 38 P. falciparum proteins putatively involved in naturally acquired immunity to malaria in 195 young children participating in a case-control study nested within the African phase 3 clinical trial of RTS,S/AS01E (MAL055 NCT00866619) in two sites of different transmission intensity (Kintampo high and Manhiça moderate/low). We measured antibody levels by quantitative suspension array technology and applied regression models, multimarker analysis, and machine learning techniques to analyze factors affecting their levels and correlates of protection. Results: RTS,S/AS01E immunization decreased antibody responses to parasite antigens considered as markers of exposure (MSP142, AMA1) and levels correlated with risk of clinical malaria over 1-year follow-up. In addition, we show for the first time that RTS,S vaccination increased IgG levels to a specific group of pre-erythrocytic and blood-stage antigens (MSP5, MSP1 block 2, RH4.2, EBA140, and SSP2/TRAP) which levels correlated with protection against clinical malaria (odds ratio [95% confidence interval] 0.53 [0.3–0.93], p = 0.03, for MSP1; 0.52 [0.26–0.98], p = 0.05, for SSP2) in multivariable logistic regression analyses. Conclusions: Increased antibody responses to specific P. falciparum antigens in subjects immunized with this partially efficacious vaccine upon natural infection may contribute to overall protective immunity against malaria. Inclusion of such antigens in multivalent constructs could result in more efficacious second-generation multistage vaccines.
publishDate	2019
dc.date.none.fl_str_mv	2019 2019 2019 2019
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/2445/139548
url	https://hdl.handle.net/2445/139548
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: http://dx.doi.org/10.1186/s12916-019-1378-6 BMC Medicine, 2019, vol. 17 http://dx.doi.org/10.1186/s12916-019-1378-6
dc.rights.none.fl_str_mv	cc by (c) Dobaño et al., 2019 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc by (c) Dobaño et al., 2019 http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	19 p. application/pdf
dc.publisher.none.fl_str_mv	BioMed Central
publisher.none.fl_str_mv	BioMed Central
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
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repository.mail.fl_str_mv
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RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study

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