A T cell-targeted multi-antigen vaccine generates robust cellular and humoral immunity against SARS-CoV-2 infection.

Autor:	Boulton S; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Poutou J; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Gill R; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Alluqmani N; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., He X; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Singaravelu R; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Crupi MJF; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Petryk J; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Austin B; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Angka L; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Taha Z; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Teo I; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Singh S; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Jamil R; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Marius R; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Martin N; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Jamieson T; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Azad T; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Faculty of Medicine and Health Sciences, Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada.; Centre de Recherche du CHUS, Sherbrooke, QC J1H 5N4, Canada., Diallo JS; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Ilkow CS; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Bell JC; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2023 Sep 16; Vol. 31, pp. 101110. Date of Electronic Publication: 2023 Sep 16 (Print Publication: 2023).
DOI:	10.1016/j.omtm.2023.101110
Abstrakt:	SARS-CoV-2, the etiological agent behind the coronavirus disease 2019 (COVID-19) pandemic, has continued to mutate and create new variants with increased resistance against the WHO-approved spike-based vaccines. With a significant portion of the worldwide population still unvaccinated and with waning immunity against newly emerging variants, there is a pressing need to develop novel vaccines that provide broader and longer-lasting protection. To generate broader protective immunity against COVID-19, we developed our second-generation vaccinia virus-based COVID-19 vaccine, TOH-VAC-2, encoded with modified versions of the spike (S) and nucleocapsid (N) proteins as well as a unique poly-epitope antigen that contains immunodominant T cell epitopes from seven different SARS-CoV-2 proteins. We show that the poly-epitope antigen restimulates T cells from the PBMCs of individuals formerly infected with SARS-CoV-2. In mice, TOH-VAC-2 vaccination produces high titers of S- and N-specific antibodies and generates robust T cell immunity against S, N, and poly-epitope antigens. The immunity generated from TOH-VAC-2 is also capable of protecting mice from heterologous challenge with recombinant VSV viruses that express the same SARS-CoV-2 antigens. Altogether, these findings demonstrate the effectiveness of our versatile vaccine platform as an alternative or complementary approach to current vaccines. Competing Interests: All authors have declared that they have no conflicts of interest with this study. (© 2023 The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu