Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium

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  • dc.contributor.author Marcos Villar, Laura
  • dc.contributor.author Meyerhans, Andreas
  • dc.contributor.author Gómez, Carmen Elena
  • dc.date.accessioned 2024-09-19T06:05:55Z
  • dc.date.available 2024-09-19T06:05:55Z
  • dc.date.issued 2024
  • dc.description.abstract Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.
  • dc.description.sponsorship This investigation was supported by Preclinical development of innovative mRNA/MVA vaccines against SARS-CoV-2, COVARNA Consortium, Instituto de Salud Carlos III and Generalitat de Catalunya, La CaixaImpulse grant CF01-00008 and Ferrovial and MAPFRE donations (to ME). We also acknowledge financial support from the Spanish State Research Agency, AEI/10.13039/501100011033, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2013-0347, SEV-2017-0712). This study was partially supported by grants from the Spanish State Research Agency (PID2020-117425RB-C22), the Instituto de Salud Carlos III (grants: COV20/00214; ICI20/00067; FIS PI18/00699; FIS PI22/00814), the Fondo Europeo para el Desarrollo Regional (FEDER) the CERCA Programme/Generalitat de Catalunya SGR 615 and SGR 653, Competitive Reference Groups, Consellería de Educación e Ordenación Universitaria, Xunta de Galicia, Ref: ED431C 2021/17 and the European Union (European Regional Development Fund - ERDF) “ REF: ED431G 2019/02”.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Marcos-Villar L, Perdiguero B, López-Bravo M, Zamora C, Sin L, Álvarez E, et al. Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium. Emerg Microbes Infect. 2024 Dec;13(1):2387906. DOI: 10.1080/22221751.2024.2387906
  • dc.identifier.doi http://dx.doi.org/10.1080/22221751.2024.2387906
  • dc.identifier.issn 2222-1751
  • dc.identifier.uri http://hdl.handle.net/10230/61154
  • dc.language.iso eng
  • dc.publisher Taylor & Francis
  • dc.relation.ispartof Emerg Microbes Infect. 2024 Dec;13(1):2387906
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-117425RB-C22
  • dc.rights © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword SARS-CoV-2 vaccine
  • dc.subject.keyword mRNA/MVA regimen
  • dc.subject.keyword Nanocarriers
  • dc.subject.keyword Trimeric-RBD
  • dc.subject.keyword Vaccine protection
  • dc.title Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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