Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen

Development of a vaccine against HIV remains a major target goal in the field. The recent success of mRNA vaccines against the coronavirus SARS-CoV-2 is pointing out a new era of vaccine designs against pathogens. Here, we have generated two types of mRNA vaccine candidates against HIV-1; one based...

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Autores: Gómez, Carmen E., Perdiguero, Beatriz, Usero, Lorena, Marcos-Villar, Laura, Miralles, Laia, Leal, Lorna, Sorzano, Carlos Óscar S., Sánchez-Corzo, Cristina, Plana, Montserrat, García, Felipe, Esteban, Mariano
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/253469
Acceso en línea:http://hdl.handle.net/10261/253469
Access Level:acceso abierto
Palabra clave:HIV-1 mRNA vaccines
Multiepitopic protein
Intranodal delivery
T cells
Poxvirus MVA vector
Mice
Combined vaccines
Prime/boost
Immune responses
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oai_identifier_str oai:digital.csic.es:10261/253469
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
title Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
spellingShingle Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
Gómez, Carmen E.
HIV-1 mRNA vaccines
Multiepitopic protein
Intranodal delivery
T cells
Poxvirus MVA vector
Mice
Combined vaccines
Prime/boost
Immune responses
title_short Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
title_full Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
title_fullStr Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
title_full_unstemmed Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
title_sort Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
dc.creator.none.fl_str_mv Gómez, Carmen E.
Perdiguero, Beatriz
Usero, Lorena
Marcos-Villar, Laura
Miralles, Laia
Leal, Lorna
Sorzano, Carlos Óscar S.
Sánchez-Corzo, Cristina
Plana, Montserrat
García, Felipe
Esteban, Mariano
author Gómez, Carmen E.
author_facet Gómez, Carmen E.
Perdiguero, Beatriz
Usero, Lorena
Marcos-Villar, Laura
Miralles, Laia
Leal, Lorna
Sorzano, Carlos Óscar S.
Sánchez-Corzo, Cristina
Plana, Montserrat
García, Felipe
Esteban, Mariano
author_role author
author2 Perdiguero, Beatriz
Usero, Lorena
Marcos-Villar, Laura
Miralles, Laia
Leal, Lorna
Sorzano, Carlos Óscar S.
Sánchez-Corzo, Cristina
Plana, Montserrat
García, Felipe
Esteban, Mariano
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Commission
Instituto de Salud Carlos III
Generalitat de Catalunya
Gómez, Carmen E. [0000-0002-5414-7935]
Leal, Lorna [0000-0001-7887-6027]
Sorzano, Carlos Óscar S. [0000-0002-9473-283X]
García, Felipe [0000-0001-7658-5832]
Esteban, Mariano [0000-0003-0846-2827]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv HIV-1 mRNA vaccines
Multiepitopic protein
Intranodal delivery
T cells
Poxvirus MVA vector
Mice
Combined vaccines
Prime/boost
Immune responses
topic HIV-1 mRNA vaccines
Multiepitopic protein
Intranodal delivery
T cells
Poxvirus MVA vector
Mice
Combined vaccines
Prime/boost
Immune responses
description Development of a vaccine against HIV remains a major target goal in the field. The recent success of mRNA vaccines against the coronavirus SARS-CoV-2 is pointing out a new era of vaccine designs against pathogens. Here, we have generated two types of mRNA vaccine candidates against HIV-1; one based on unmodified vectors and the other on 1-methyl-3′-pseudouridylyl modified vectors expressing a T cell multiepitopic construct including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (referred to as RNA-TMEP and RNA-TMEPmod, respectively) and defined their biological and immunological properties in cultured cells and in mice. In cultured cells, both mRNA vectors expressed the corresponding protein, with higher levels observed in the unmodified mRNA, leading to activated macrophages with differential induction of innate immune molecules. In mice, intranodal administration of the mRNAs induced the activation of specific T cell (CD4 and CD8) responses, and the levels were markedly enhanced after a booster immunization with the poxvirus vector MVA-TMEP expressing the same antigen. This immune activation was maintained even three months later. These findings revealed a potent combined immunization regimen able to enhance the HIV-1-specific immune responses induced by an mRNA vaccine that might be applicable to human vaccination programs with mRNA and MVA vectors.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/253469
url http://hdl.handle.net/10261/253469
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-66193-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF-2017-88089-R
SAF-2017-88089-R/AEI/10.13039/501100011033
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info:eu-repo/grantAgreement/EC/FP7/602570
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https://doi.org/10.3390/vaccines9090959
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same AntigenGómez, Carmen E.Perdiguero, BeatrizUsero, LorenaMarcos-Villar, LauraMiralles, LaiaLeal, LornaSorzano, Carlos Óscar S.Sánchez-Corzo, CristinaPlana, MontserratGarcía, FelipeEsteban, MarianoHIV-1 mRNA vaccinesMultiepitopic proteinIntranodal deliveryT cellsPoxvirus MVA vectorMiceCombined vaccinesPrime/boostImmune responsesDevelopment of a vaccine against HIV remains a major target goal in the field. The recent success of mRNA vaccines against the coronavirus SARS-CoV-2 is pointing out a new era of vaccine designs against pathogens. Here, we have generated two types of mRNA vaccine candidates against HIV-1; one based on unmodified vectors and the other on 1-methyl-3′-pseudouridylyl modified vectors expressing a T cell multiepitopic construct including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (referred to as RNA-TMEP and RNA-TMEPmod, respectively) and defined their biological and immunological properties in cultured cells and in mice. In cultured cells, both mRNA vectors expressed the corresponding protein, with higher levels observed in the unmodified mRNA, leading to activated macrophages with differential induction of innate immune molecules. In mice, intranodal administration of the mRNAs induced the activation of specific T cell (CD4 and CD8) responses, and the levels were markedly enhanced after a booster immunization with the poxvirus vector MVA-TMEP expressing the same antigen. This immune activation was maintained even three months later. These findings revealed a potent combined immunization regimen able to enhance the HIV-1-specific immune responses induced by an mRNA vaccine that might be applicable to human vaccination programs with mRNA and MVA vectors.This study was partially supported by grants from the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, SAF-2017-88089-R, RTI2018-096309-B-I00); the Fondo Europeo para el Desarrollo Regional (FEDER); the SPANISH AIDS Research Network RD16/0025/0002 and RD16/0025/0014-ISCIII-FEDER (RIS); the Fondo de Investigación Sanitaria (FIS) AC16/00051 and PI18/00699; the Instituto de Salud Carlos III (grants: COV20/00214; ICI20/00067) and the CERCA Programme/Generalitat de Catalunya SGR 615 and SGR 653. This manuscript was funded by the European Commission [grant numbers: FP7-HEALTH-2013-INNOVATION-1 602570-2, H2020-SC1- 2016-2017 (H2020-SC1-2016-RTD) Proposal: 731626-HIVACAR].Peer reviewedMolecular Diversity Preservation InternationalMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European CommissionInstituto de Salud Carlos IIIGeneralitat de CatalunyaGómez, Carmen E. [0000-0002-5414-7935]Leal, Lorna [0000-0001-7887-6027]Sorzano, Carlos Óscar S. [0000-0002-9473-283X]García, Felipe [0000-0001-7658-5832]Esteban, Mariano [0000-0003-0846-2827]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/253469reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-66193-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF-2017-88089-RSAF-2017-88089-R/AEI/10.13039/501100011033info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096309-B-I00RTI2018-096309-B-I00/AEI/10.13039/501100011033info:eu-repo/grantAgreement/EC/FP7/602570info:eu-repo/grantAgreement/EC/H2020/731626https://doi.org/10.3390/vaccines9090959Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2534692026-05-22T06:33:51Z
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