Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle...

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Autores: Gutiérrez-Álvarez, J, Honrubia, José M., Sanz-Bravo, Alejandro, González-Miranda, E., Fernandez-Delgado, Raúl, Rejas, M. Teresa, Zúñiga Lucas, Sonia, Solá Gurpegui, Isabel, Enjuanes Sánchez, Luis
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:10261/267022
Acceso en línea:http://hdl.handle.net/10261/267022
Access Level:acceso abierto
Palabra clave:Coronavirus
MERS-CoV
Vaccine
RNA replicon
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repository_id_str
spelling Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.Gutiérrez-Álvarez, JHonrubia, José M.Sanz-Bravo, AlejandroGonzález-Miranda, E.Fernandez-Delgado, RaúlRejas, M. TeresaZúñiga Lucas, SoniaSolá Gurpegui, IsabelEnjuanes Sánchez, LuisCoronavirusMERS-CoVVaccineRNA repliconSelf-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation- defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidatesGovernment of Spain and European Union co-financed grant BIO2016-75549-R; by Government of Spain grants PID2019-107001RB-I00, Proyecto Intramural Especial (PIE) 202020E079, and PIE–Consejo Superior de Investigaciones Científicas (CSIC) 202020E043; by European Commission grants ZAPI_IMI_JU_115760, ISOLDA_848166, and MANCO_101003651; and by IH grant 2P01AI060699National Academy of Sciences (U.S.)Ministerio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/267022reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1073/pnas.2111075118Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2670222026-05-22T06:33:51Z
dc.title.none.fl_str_mv Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
title Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
spellingShingle Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
Gutiérrez-Álvarez, J
Coronavirus
MERS-CoV
Vaccine
RNA replicon
title_short Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
title_full Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
title_fullStr Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
title_full_unstemmed Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
title_sort Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.
dc.creator.none.fl_str_mv Gutiérrez-Álvarez, J
Honrubia, José M.
Sanz-Bravo, Alejandro
González-Miranda, E.
Fernandez-Delgado, Raúl
Rejas, M. Teresa
Zúñiga Lucas, Sonia
Solá Gurpegui, Isabel
Enjuanes Sánchez, Luis
author Gutiérrez-Álvarez, J
author_facet Gutiérrez-Álvarez, J
Honrubia, José M.
Sanz-Bravo, Alejandro
González-Miranda, E.
Fernandez-Delgado, Raúl
Rejas, M. Teresa
Zúñiga Lucas, Sonia
Solá Gurpegui, Isabel
Enjuanes Sánchez, Luis
author_role author
author2 Honrubia, José M.
Sanz-Bravo, Alejandro
González-Miranda, E.
Fernandez-Delgado, Raúl
Rejas, M. Teresa
Zúñiga Lucas, Sonia
Solá Gurpegui, Isabel
Enjuanes Sánchez, Luis
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Coronavirus
MERS-CoV
Vaccine
RNA replicon
topic Coronavirus
MERS-CoV
Vaccine
RNA replicon
description Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation- defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
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/10261/267022
url http://hdl.handle.net/10261/267022
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1073/pnas.2111075118
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences (U.S.)
publisher.none.fl_str_mv National Academy of Sciences (U.S.)
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
repository.mail.fl_str_mv
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score 15,812429

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