B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2

Perdiguero de la Torre, Beatriz; Falqui, Michela Maria Eugenia; Coloma Ciudad, Rocío; Álvarez, Enrique; Marcos-Villar, Laura; Sin, Laura; López-Bravo, María; Valverde, José Ramón; Sorzano, Carlos Óscar S.; Esteban, Mariano; Guerra García, María Susana; Gómez, Carmen Elena

B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2

Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for vaccines targeting both neutralizing antibodies (NAbs) and long-lasting cross-reactive T cells covering multiple viral proteins to provide broad and durable protection against emerging variants. Methods: To address...

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Autores:	Perdiguero de la Torre, Beatriz, Falqui, Michela Maria Eugenia, Coloma Ciudad, Rocío, Álvarez, Enrique, Marcos-Villar, Laura, Sin, Laura, López-Bravo, María, Valverde, José Ramón, Sorzano, Carlos Óscar S., Esteban, Mariano, Guerra García, María Susana, Gómez, Carmen Elena
Tipo de recurso:	artículo
Fecha de publicación:	2024
País:	España
Institución:	Universidad Autónoma de Madrid
Repositorio:	Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:	inglés
OAI Identifier:	oai:repositorio.uam.es:10486/720904
Acceso en línea:	http://hdl.handle.net/10486/720904 https://dx.doi.org/10.3390/vaccines12111213
Access Level:	acceso abierto
Palabra clave:	cellular response DNA and MVA vectors efficacy in mice immunogenicity innate response ISG15 adjuvant multiepitopic protein SARS-CoV-2 vaccine Medicina

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spelling	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2Perdiguero de la Torre, BeatrizFalqui, Michela Maria EugeniaColoma Ciudad, RocíoÁlvarez, EnriqueMarcos-Villar, LauraSin, LauraLópez-Bravo, MaríaValverde, José RamónSorzano, Carlos Óscar S.Esteban, MarianoGuerra García, María SusanaGómez, Carmen Elenacellular responseDNA and MVA vectorsefficacy in miceimmunogenicityinnate responseISG15 adjuvantmultiepitopic proteinSARS-CoV-2vaccineMedicinaBackground: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for vaccines targeting both neutralizing antibodies (NAbs) and long-lasting cross-reactive T cells covering multiple viral proteins to provide broad and durable protection against emerging variants. Methods: To address this, here we developed two vaccine candidates, namely (i) DNA-CoV2-TMEP, expressing the multiepitopic CoV2-TMEP protein containing immunodominant and conserved T cell regions from SARS-CoV-2 structural proteins, and (ii) MVA-CoV2-B2AT, encoding a bi-cistronic multiepitopic construct that combines conserved B and T cell overlapping regions from SARS-CoV-2 structural proteins. Results: Both candidates were assessed in vitro and in vivo demonstrating their ability to induce robust immune responses. In C57BL/6 mice, DNA-CoV2-TMEP enhanced the recruitment of innate immune cells and stimulated SARS-CoV-2-specific polyfunctional T cells targeting multiple viral proteins. MVA-CoV2-B2AT elicited NAbs against various SARS-CoV-2 variants of concern (VoCs) and reduced viral replication and viral yields against the Beta variant in susceptible K18-hACE2 mice. The combination of MVA-CoV2-B2AT with a mutated ISG15 form as an adjuvant further increased the magnitude, breadth and polyfunctional profile of the response. Conclusion: These findings underscore the potential of these multiepitopic proteins when expressed from DNA or MVA vectors to provide protection against SARS-CoV-2 and its variants, supporting their further development as next-generation COVID-19 vaccinesThis research was supported by La Caixa Banking Foundation, grant CF01-00008; Spanish Ministry of Science and Innovation (MCIN)/Spanish Research Agency, grants PID2020-117425RB-C21, PID2020-117425RB-C22 and PDC2021-121307-100; Fondo COVID-19, grant COV20/00151 (Spanish Health Ministry and ISCIII); CSIC, grant 2020E84; and Ferrovial donations (to M.E.)MDPIDepartamento de Medicina Preventiva y Salud Pública y MicrobiologíaFacultad de Medicina20242024-11-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/720904https://dx.doi.org/10.3390/vaccines12111213reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7209042026-06-23T12:46:27Z
dc.title.none.fl_str_mv	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
title	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
spellingShingle	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2 Perdiguero de la Torre, Beatriz cellular response DNA and MVA vectors efficacy in mice immunogenicity innate response ISG15 adjuvant multiepitopic protein SARS-CoV-2 vaccine Medicina
title_short	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
title_full	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
title_fullStr	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
title_full_unstemmed	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
title_sort	B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2
dc.creator.none.fl_str_mv	Perdiguero de la Torre, Beatriz Falqui, Michela Maria Eugenia Coloma Ciudad, Rocío Álvarez, Enrique Marcos-Villar, Laura Sin, Laura López-Bravo, María Valverde, José Ramón Sorzano, Carlos Óscar S. Esteban, Mariano Guerra García, María Susana Gómez, Carmen Elena
author	Perdiguero de la Torre, Beatriz
author_facet	Perdiguero de la Torre, Beatriz Falqui, Michela Maria Eugenia Coloma Ciudad, Rocío Álvarez, Enrique Marcos-Villar, Laura Sin, Laura López-Bravo, María Valverde, José Ramón Sorzano, Carlos Óscar S. Esteban, Mariano Guerra García, María Susana Gómez, Carmen Elena
author_role	author
author2	Falqui, Michela Maria Eugenia Coloma Ciudad, Rocío Álvarez, Enrique Marcos-Villar, Laura Sin, Laura López-Bravo, María Valverde, José Ramón Sorzano, Carlos Óscar S. Esteban, Mariano Guerra García, María Susana Gómez, Carmen Elena
author2_role	author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Departamento de Medicina Preventiva y Salud Pública y Microbiología Facultad de Medicina
dc.subject.none.fl_str_mv	cellular response DNA and MVA vectors efficacy in mice immunogenicity innate response ISG15 adjuvant multiepitopic protein SARS-CoV-2 vaccine Medicina
topic	cellular response DNA and MVA vectors efficacy in mice immunogenicity innate response ISG15 adjuvant multiepitopic protein SARS-CoV-2 vaccine Medicina
description	Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for vaccines targeting both neutralizing antibodies (NAbs) and long-lasting cross-reactive T cells covering multiple viral proteins to provide broad and durable protection against emerging variants. Methods: To address this, here we developed two vaccine candidates, namely (i) DNA-CoV2-TMEP, expressing the multiepitopic CoV2-TMEP protein containing immunodominant and conserved T cell regions from SARS-CoV-2 structural proteins, and (ii) MVA-CoV2-B2AT, encoding a bi-cistronic multiepitopic construct that combines conserved B and T cell overlapping regions from SARS-CoV-2 structural proteins. Results: Both candidates were assessed in vitro and in vivo demonstrating their ability to induce robust immune responses. In C57BL/6 mice, DNA-CoV2-TMEP enhanced the recruitment of innate immune cells and stimulated SARS-CoV-2-specific polyfunctional T cells targeting multiple viral proteins. MVA-CoV2-B2AT elicited NAbs against various SARS-CoV-2 variants of concern (VoCs) and reduced viral replication and viral yields against the Beta variant in susceptible K18-hACE2 mice. The combination of MVA-CoV2-B2AT with a mutated ISG15 form as an adjuvant further increased the magnitude, breadth and polyfunctional profile of the response. Conclusion: These findings underscore the potential of these multiepitopic proteins when expressed from DNA or MVA vectors to provide protection against SARS-CoV-2 and its variants, supporting their further development as next-generation COVID-19 vaccines
publishDate	2024
dc.date.none.fl_str_mv	2024 2024-11-01
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10486/720904 https://dx.doi.org/10.3390/vaccines12111213
url	http://hdl.handle.net/10486/720904 https://dx.doi.org/10.3390/vaccines12111213
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	MDPI
publisher.none.fl_str_mv	MDPI
dc.source.none.fl_str_mv	reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid
instname_str	Universidad Autónoma de Madrid
reponame_str	Biblos-e Archivo. Repositorio Institucional de la UAM
collection	Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,811543

B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2

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