ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2

[Background] Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One...

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Detalhes bibliográficos
Autores: García-Arriaza, Juan, Falqui, Michela, Pérez, Patricia, Coloma, Rocío, Perdiguero, Beatriz, Álvarez, Enrique, Marcos-Villar, Laura, Astorgano, David, Campaña Gómez, Irene, Sorzano, Carlos Óscar S., Esteban, Mariano, Gómez, Carmen E., Guerra, Susana
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/394177
Acesso em linha:http://hdl.handle.net/10261/394177
Access Level:acceso abierto
Palavra-chave:ISG15
Adjuvant
Vaccines
MVA
ZIKV
SARS-CoV-2
Innate immunity
T-cell responses
id ES_aea81f6842e807385a2dc88e9f62206b
oai_identifier_str oai:digital.csic.es:10261/394177
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
title ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
spellingShingle ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
García-Arriaza, Juan
ISG15
Adjuvant
Vaccines
MVA
ZIKV
SARS-CoV-2
Innate immunity
T-cell responses
title_short ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
title_full ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
title_fullStr ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
title_full_unstemmed ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
title_sort ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2
dc.creator.none.fl_str_mv García-Arriaza, Juan
Falqui, Michela
Pérez, Patricia
Coloma, Rocío
Perdiguero, Beatriz
Álvarez, Enrique
Marcos-Villar, Laura
Astorgano, David
Campaña Gómez, Irene
Sorzano, Carlos Óscar S.
Esteban, Mariano
Gómez, Carmen E.
Guerra, Susana
author García-Arriaza, Juan
author_facet García-Arriaza, Juan
Falqui, Michela
Pérez, Patricia
Coloma, Rocío
Perdiguero, Beatriz
Álvarez, Enrique
Marcos-Villar, Laura
Astorgano, David
Campaña Gómez, Irene
Sorzano, Carlos Óscar S.
Esteban, Mariano
Gómez, Carmen E.
Guerra, Susana
author_role author
author2 Falqui, Michela
Pérez, Patricia
Coloma, Rocío
Perdiguero, Beatriz
Álvarez, Enrique
Marcos-Villar, Laura
Astorgano, David
Campaña Gómez, Irene
Sorzano, Carlos Óscar S.
Esteban, Mariano
Gómez, Carmen E.
Guerra, Susana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España)
García-Arriaza, Juan [0000-0002-5167-5724]
Pérez, Patricia [0000-0001-8983-6784]
Coloma, Rocío [0000-0003-0365-1565]
Perdiguero, Beatriz [0000-0001-6276-7766]
Álvarez, Enrique [0000-0001-8308-7524]
Astorgano, David [0000-0002-2969-1840]
Campaña Gómez, Irene [0000-0002-8073-8114]
Sorzano, Carlos Óscar S. [0000-0002-9473-283X]
Esteban, Mariano [0000-0003-0846-2827]
Gómez, Carmen E. [0000-0002-5414-7935]
Guerra, Susana [0000-0001-9067-2991]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv ISG15
Adjuvant
Vaccines
MVA
ZIKV
SARS-CoV-2
Innate immunity
T-cell responses
topic ISG15
Adjuvant
Vaccines
MVA
ZIKV
SARS-CoV-2
Innate immunity
T-cell responses
description [Background] Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated gene 15 (ISG15), a key modulator of antiviral immunity that acts both through ISGylation-dependent mechanisms and as a cytokine-like molecule.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
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/10261/394177
url http://hdl.handle.net/10261/394177
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #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 2013-2016/SAF2017-88089-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PDC2021-121307-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117425RB-C22
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/vaccines13070696
https://doi.org/10.3390/vaccines13070696
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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
repository.name.fl_str_mv
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spelling ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2García-Arriaza, JuanFalqui, MichelaPérez, PatriciaColoma, RocíoPerdiguero, BeatrizÁlvarez, EnriqueMarcos-Villar, LauraAstorgano, DavidCampaña Gómez, IreneSorzano, Carlos Óscar S.Esteban, MarianoGómez, Carmen E.Guerra, SusanaISG15AdjuvantVaccinesMVAZIKVSARS-CoV-2Innate immunityT-cell responses[Background] Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated gene 15 (ISG15), a key modulator of antiviral immunity that acts both through ISGylation-dependent mechanisms and as a cytokine-like molecule.[Methods] In this study, we assessed the immunostimulatory potential of ISG15 as an adjuvant in Modified Vaccinia virus Ankara (MVA)-based vaccine candidates targeting Zika virus (ZIKV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Early innate responses and immune cell infiltration were analyzed in immunized mice by flow cytometry and cytokine profiling. To elucidate the underlying mechanism of action of ISG15, in vitro co-infection studies were performed in macrophages. Finally, we evaluated the magnitude and functional quality of the elicited antigen-specific cellular immune responses in vivo.[Results] Analysis of early innate responses revealed both platform- and variant-specific effects. ISG15AA preferentially promoted natural killer (NK) cell recruitment at the injection site, whereas ISG15GG enhanced myeloid cell infiltration in draining lymph nodes (DLNs), particularly when delivered via MVA. Moreover, in vitro co-infection of macrophages with MVA-based vaccine vectors and the ISG15AA mutant led to a marked increase in proinflammatory cytokine production, highlighting a dominant role for the extracellular, ISGylation-independent functions of ISG15 in shaping vaccine-induced immunity. Notably, co-infection of ISG15 with MVA-ZIKV and MVA-SARS-CoV-2 vaccine candidates enhanced the magnitude of antigen-specific immune responses in both vaccine models.[Conclusions] ISG15, particularly in its ISGylation-deficient form, acts as a promising immunomodulatory adjuvant for viral vaccines, enhancing both innate and adaptive immune responses. Consistent with previous findings in the context of Human Immunodeficiency virus type 1 (HIV-1) vaccines, this study further supports the potential of ISG15 as an effective adjuvant for vaccines targeting viral infections such as ZIKV and SARS-CoV-2.This research was supported by the Spanish State Research Agency SAF-2017-88089-R, PDC2021-121307-I00, and PID2020-117425RB-C21 to S.G; PID2020-117425RB-C22 to C.E.G; CSIC grant 202120E079 and grant CNS2022-135511, funded by the Spanish Ministry of Science, Innovation and Universities (MCIU)/Spanish Research Agency (AEI)/10.130/501100011033 and by the European Union NextGenerationEU/PRTR to promote the consolidation of research to J.G.-A; CSIC grant 2020E84 to M.E.; Spanish MCIU/AEI/10.13039/501100011033 grant PID2020-114481RB-I00 to J.G.-A. and M.E., and funds from the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), co-financed with FEDER funds to C.E.G and J.G.-A. This research work was also funded by the European Commission–NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global) (to J.G.-A. and M.E). The funders were not involved in the study design, collection, analysis, interpretation of data, writing of this article, or decision to submit it for publication.Peer reviewedMultidisciplinary Digital Publishing InstituteAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (España)García-Arriaza, Juan [0000-0002-5167-5724]Pérez, Patricia [0000-0001-8983-6784]Coloma, Rocío [0000-0003-0365-1565]Perdiguero, Beatriz [0000-0001-6276-7766]Álvarez, Enrique [0000-0001-8308-7524]Astorgano, David [0000-0002-2969-1840]Campaña Gómez, Irene [0000-0002-8073-8114]Sorzano, Carlos Óscar S. [0000-0002-9473-283X]Esteban, Mariano [0000-0003-0846-2827]Gómez, Carmen E. [0000-0002-5414-7935]Guerra, Susana [0000-0001-9067-2991]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/394177reponame: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#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-88089-Rinfo: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-C22The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/vaccines13070696https://doi.org/10.3390/vaccines13070696Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3941772026-05-22T06:33:51Z
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