An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses

The human immunodeficiency virus (HIV), responsible of the Acquired Immune Deficiency Syndrome (AIDS), continues to be a major global public health issue with any cure or vaccine available. The Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is induced by interferons and...

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Autores: Falqui, Michela, Perdiguero, Beatriz, Coloma, Rocío, Albert, Manuel, Marcos-Villar, Laura, McGrail, Joseph Patrick, Sorzano, Carlos Óscar S., Esteban, Mariano, Gómez, Carmen Elena, Guerra, Susana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/362400
Acceso en línea:http://hdl.handle.net/10261/362400
https://api.elsevier.com/content/abstract/scopus_id/85161956654
Access Level:acceso abierto
Palabra clave:HIV
IFN
ISG15
Modify Vaccinia virus Ankara
adjuvant
inmunity
vaccine
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
id ES_5fac84d8c73a81a340daadca7d8dba2c
oai_identifier_str oai:digital.csic.es:10261/362400
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
title An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
spellingShingle An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
Falqui, Michela
HIV
IFN
ISG15
Modify Vaccinia virus Ankara
adjuvant
inmunity
vaccine
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
title_short An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
title_full An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
title_fullStr An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
title_full_unstemmed An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
title_sort An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses
dc.creator.none.fl_str_mv Falqui, Michela
Perdiguero, Beatriz
Coloma, Rocío
Albert, Manuel
Marcos-Villar, Laura
McGrail, Joseph Patrick
Sorzano, Carlos Óscar S.
Esteban, Mariano
Gómez, Carmen Elena
Guerra, Susana
author Falqui, Michela
author_facet Falqui, Michela
Perdiguero, Beatriz
Coloma, Rocío
Albert, Manuel
Marcos-Villar, Laura
McGrail, Joseph Patrick
Sorzano, Carlos Óscar S.
Esteban, Mariano
Gómez, Carmen Elena
Guerra, Susana
author_role author
author2 Perdiguero, Beatriz
Coloma, Rocío
Albert, Manuel
Marcos-Villar, Laura
McGrail, Joseph Patrick
Sorzano, Carlos Óscar S.
Esteban, Mariano
Gómez, Carmen Elena
Guerra, Susana
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Sanidad (España)
Marcos-Villar, Laura [0000-0002-8635-6432]
Sorzano, Carlos Óscar S [0000-0002-9473-283X]
Esteban, Mariano [0000-0003-0846-2827]
Gómez, Carmen Elena [0000-0002-5414-7935]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv HIV
IFN
ISG15
Modify Vaccinia virus Ankara
adjuvant
inmunity
vaccine
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
topic HIV
IFN
ISG15
Modify Vaccinia virus Ankara
adjuvant
inmunity
vaccine
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
description The human immunodeficiency virus (HIV), responsible of the Acquired Immune Deficiency Syndrome (AIDS), continues to be a major global public health issue with any cure or vaccine available. The Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is induced by interferons and plays a critical role in the immune response. ISG15 is a modifier protein that covalently binds to its targets via a reversible bond, a process known as ISGylation, which is the best-characterized activity of this protein to date. However, ISG15 can also interact with intracellular proteins via non-covalent binding or act as a cytokine in the extracellular space after secretion. In previous studies we proved the adjuvant effect of ISG15 when delivered by a DNA-vector in heterologous prime-boost combination with a Modified Vaccinia virus Ankara (MVA)-based recombinant virus expressing HIV-1 antigens Env/Gag-Pol-Nef (MVA-B). Here we extended these results evaluating the adjuvant effect of ISG15 when expressed by an MVA vector. For this, we generated and characterized two novel MVA recombinants expressing different forms of ISG15, the wild-type ISG15GG (able to perform ISGylation) or the mutated ISG15AA (unable to perform ISGylation). In mice immunized with the heterologous DNA prime/MVA boost regimen, the expression of the mutant ISG15AA from MVA-Δ3-ISG15AA vector in combination with MVA-B induced an increase in the magnitude and quality of HIV-1-specific CD8 T cells as well as in the levels of IFN-I released, providing a better immunostimulatory activity than the wild-type ISG15GG. Our results confirm the importance of ISG15 as an immune adjuvant in the vaccine field and highlights its role as a potential relevant component in HIV-1 immunization protocols.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/362400
https://api.elsevier.com/content/abstract/scopus_id/85161956654
url http://hdl.handle.net/10261/362400
https://api.elsevier.com/content/abstract/scopus_id/85161956654
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117425RB-C21
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Frontiers in cellular and infection microbiology
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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)
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spelling An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responsesFalqui, MichelaPerdiguero, BeatrizColoma, RocíoAlbert, ManuelMarcos-Villar, LauraMcGrail, Joseph PatrickSorzano, Carlos Óscar S.Esteban, MarianoGómez, Carmen ElenaGuerra, SusanaHIVIFNISG15Modify Vaccinia virus Ankaraadjuvantinmunityvaccinehttp://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all agesThe human immunodeficiency virus (HIV), responsible of the Acquired Immune Deficiency Syndrome (AIDS), continues to be a major global public health issue with any cure or vaccine available. The Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is induced by interferons and plays a critical role in the immune response. ISG15 is a modifier protein that covalently binds to its targets via a reversible bond, a process known as ISGylation, which is the best-characterized activity of this protein to date. However, ISG15 can also interact with intracellular proteins via non-covalent binding or act as a cytokine in the extracellular space after secretion. In previous studies we proved the adjuvant effect of ISG15 when delivered by a DNA-vector in heterologous prime-boost combination with a Modified Vaccinia virus Ankara (MVA)-based recombinant virus expressing HIV-1 antigens Env/Gag-Pol-Nef (MVA-B). Here we extended these results evaluating the adjuvant effect of ISG15 when expressed by an MVA vector. For this, we generated and characterized two novel MVA recombinants expressing different forms of ISG15, the wild-type ISG15GG (able to perform ISGylation) or the mutated ISG15AA (unable to perform ISGylation). In mice immunized with the heterologous DNA prime/MVA boost regimen, the expression of the mutant ISG15AA from MVA-Δ3-ISG15AA vector in combination with MVA-B induced an increase in the magnitude and quality of HIV-1-specific CD8 T cells as well as in the levels of IFN-I released, providing a better immunostimulatory activity than the wild-type ISG15GG. Our results confirm the importance of ISG15 as an immune adjuvant in the vaccine field and highlights its role as a potential relevant component in HIV-1 immunization protocols.This research was supported by the Spanish State Research Agency Ministry of Health of Spain, State secretary of R+D and FEDER/FSE, SAF-2017-88089-R, PDC2021-121307-I00 PID2020- 117425RB-C21 to SG and PID2020-117425RB-C22 to CG; by CIBER consortium, Thematic Area in Infectious Diseases: CIBERINFEC (CB21/13/00108) to CG; by Red Temática de Investigación Cooperativa en Salud: Red Española de Investigación en Sida (RIS) RD16/0025/0014 and in part by European HIV Vaccine Alliance (EHVA) grant ID: 681032 to ME.Peer reviewedFrontiers MediaMinisterio de Sanidad (España)Marcos-Villar, Laura [0000-0002-8635-6432]Sorzano, Carlos Óscar S [0000-0002-9473-283X]Esteban, Mariano [0000-0003-0846-2827]Gómez, Carmen Elena [0000-0002-5414-7935]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/362400https://api.elsevier.com/content/abstract/scopus_id/85161956654reponame: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#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PDC2021-121307-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117425RB-C21info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117425RB-C22info:eu-repo/grantAgreement/MINECO//RD16%2F0025%2F0014info:eu-repo/grantAgreement/EC/H2020/681032Frontiers in cellular and infection microbiologyapplication/pdfSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3624002026-05-22T06:33:51Z
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