Assessment of Human SARS CoV-2-Specific T-Cell Responses Elicited In Vitro by New Computationally Designed mRNA Immunogens (COVARNA)
Ignasi Esteban,
Carmen Pastor-Quiñones,
Lorena Usero,
Elena Aurrecoechea,
Lorenzo Franceschini,
Arthur Esprit,
Josep Lluís Gelpí,
Francisco Martínez-Jiménez,
Núria López-Bigas,
Karine Breckpot,
Kris Thielemans,
Lorna Leal,
Carmen Elena Gómez,
Marta Sisteré-Oró,
Andreas Meyerhans,
Mariano Esteban,
María José Alonso,
Felipe García,
Montserrat Plana
Affiliations
Ignasi Esteban
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Carmen Pastor-Quiñones
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Lorena Usero
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Elena Aurrecoechea
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Lorenzo Franceschini
Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium
Arthur Esprit
Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium
Josep Lluís Gelpí
Department of Biochemistry and Molecular Biomedicine, University of Barcelona, 08028 Barcelona, Spain
Francisco Martínez-Jiménez
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
Núria López-Bigas
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
Karine Breckpot
Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium
Kris Thielemans
Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium
Lorna Leal
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Carmen Elena Gómez
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
Marta Sisteré-Oró
Infection Biology Laboratory, Department of Medicine and Life Sciences, Pompeu Fabra University, 08003 Barcelona, Spain
Andreas Meyerhans
Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
Mariano Esteban
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
María José Alonso
Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Campus Vida, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Felipe García
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Montserrat Plana
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
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.
