Assessment of human SARS CoV-2-Specific T-Cell responses elicited In Vitro by new computationally designed mRNA immunogens (COVARNA)

Esteban, Ignasi; Pastor-Quiñones, Carmen; Usero, Lorena; Aurrecoechea, Elena; Franceschini, Lorenzo; Esprit, Arthur; Gelpí, Josep Lluís; Martínez-Jiménez, Francisco, 1988-; López Bigas, Núria; Breckpot, Karine; Thielemans, Kris; Leal, Lorna; Gómez, Carmen Elena; Sisteré-Oró, Marta; Meyerhans, Andreas; Esteban, Mariano; Alonso Fernández, María José; García, Felipe; Plana, Montserrat; COVARNA Consortium

Assessment of human SARS CoV-2-Specific T-Cell responses elicited In Vitro by new computationally designed mRNA immunogens (COVARNA)

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dc.contributor.author Esteban, Ignasi
dc.contributor.author Pastor-Quiñones, Carmen
dc.contributor.author Usero, Lorena
dc.contributor.author Aurrecoechea, Elena
dc.contributor.author Franceschini, Lorenzo
dc.contributor.author Esprit, Arthur
dc.contributor.author Gelpí, Josep Lluís
dc.contributor.author Martínez-Jiménez, Francisco, 1988-
dc.contributor.author López Bigas, Núria
dc.contributor.author Breckpot, Karine
dc.contributor.author Thielemans, Kris
dc.contributor.author Leal, Lorna
dc.contributor.author Gómez, Carmen Elena
dc.contributor.author Sisteré-Oró, Marta
dc.contributor.author Meyerhans, Andreas
dc.contributor.author Esteban, Mariano
dc.contributor.author Alonso Fernández, María José
dc.contributor.author García, Felipe
dc.contributor.author Plana, Montserrat
dc.contributor.author COVARNA Consortium
dc.date.accessioned 2024-04-16T06:28:38Z
dc.date.available 2024-04-16T06:28:38Z
dc.date.issued 2023
dc.description.abstract The COVID-19 pandemic has brought significant changes and advances in the field of vaccination, including the implementation and widespread use of encapsidated mRNA vaccines in general healthcare practice. Here, we present two new mRNAs expressing antigenic parts of the SARS-CoV-2 spike protein and provide data supporting their functionality. The first mRNA, called RBD-mRNA, encodes a trimeric form of the virus spike protein receptor binding domain (RBD). The other mRNA, termed T-mRNA, codes for the relevant HLA I and II spike epitopes. The two mRNAs (COVARNA mRNAs) were designed to be used for delivery to cells in combination, with the RBD-mRNA being the primary source of antigen and the T-mRNA working as an enhancer of immunogenicity by supporting CD4 and CD8 T-cell activation. This innovative approach substantially differs from other available mRNA vaccines, which are largely directed to antibody production by the entire spike protein. In this study, we first show that both mRNAs are functionally transfected into human antigen-presenting cells (APCs). We obtained peripheral blood mononuclear cell (PBMC) samples from three groups of voluntary donors differing in their immunity against SARS-CoV-2: non-infected (naïve), infected-recovered (convalescent), and vaccinated. Using an established method of co-culturing autologous human dendritic cells (hDCs) with T-cells, we detected proliferation and cytokine secretion, thus demonstrating the ability of the COVARNA mRNAs to activate T-cells in an antigen-specific way. Interestingly, important differences in the intensity of the response between the infected-recovered (convalescent) and vaccinated donors were observed, with the levels of T-cell proliferation and cytokine secretion (IFNγ, IL-2R, and IL-13) being higher in the vaccinated group. In summary, our data support the further study of these mRNAs as a combined approach for future use as a vaccine.
dc.description.sponsorship This study was partially supported by grants from the Spanish Ministry of Economy (MINECO) (grants: SAF-2017-88089-R and RTI2018-096309-B-I00); the Fondo Europeo para el Desarrollo Regional (FEDER); the SPANISH AIDS Research Network RD16/0025/0002 and RD16/0025/0014-ISCIII-FEDER (RIS); projects FIS PI18/00699, COV20/00214, FIS PI22/00814, and ICI20/00067 financed by the Instituto de Salud Carlos III (ISCIII) and co-financed by the European Union; the HIVACAT program; the CERCA Programme/Generalitat de Catalunya SGR 615 and SGR 653; and by the European Commission [grant numbers: FP7-HEALTH-2013-INNOVATION-1 602570-2 and H2020-SC1-2016-2017 (H2020-SC1-2016-RTD) Proposal: 731626-HIVACAR].
dc.format.mimetype application/pdf
dc.identifier.citation Esteban I, Pastor-Quiñones C, Usero L, Aurrecoechea E, Franceschini L, Esprit A, et al. Assessment of human SARS CoV-2-Specific T-Cell responses elicited In Vitro by new computationally designed mRNA immunogens (COVARNA). Vaccines (Basel). 2023 Dec 22;12(1):15. DOI: 10.3390/vaccines12010015
dc.identifier.doi http://dx.doi.org/10.3390/vaccines12010015
dc.identifier.issn 2076-393X
dc.identifier.uri http://hdl.handle.net/10230/59782
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Vaccines (Basel). 2023 Dec 22;12(1):15
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602570
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-88089-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096309-B-I00
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/731626
dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword SARS-CoV-2
dc.subject.keyword T-cell
dc.subject.keyword Dendritic cells
dc.subject.keyword mRNA
dc.subject.keyword Vaccine
dc.title Assessment of human SARS CoV-2-Specific T-Cell responses elicited In Vitro by new computationally designed mRNA immunogens (COVARNA)
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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