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

Stephen Boulton; Joanna Poutou; Rida Gill; Nouf Alluqmani; Xiaohong He; Ragunath Singaravelu; Mathieu J F Crupi; Julia Petryk; Bradley Austin; Leonard Angka; Zaid Taha; Iris Teo; Siddarth Singh; Rameen Jamil; Ricardo Marius; Nikolas Martin; Taylor Jamieson; Taha Azad; Jean-Simon Diallo; Carolina S Ilkow; John C Bell

doi:10.1016/j.omtm.2023.101110

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

Mol Ther Methods Clin Dev. 2023 Sep 16:31:101110. doi: 10.1016/j.omtm.2023.101110. eCollection 2023 Dec 14.

Authors

Stephen Boulton^{1

2}, Joanna Poutou^{1

2}, Rida Gill¹, Nouf Alluqmani^{1

2}, Xiaohong He¹, Ragunath Singaravelu^{1

2}, Mathieu J F Crupi^{1

2}, Julia Petryk¹, Bradley Austin¹, Leonard Angka¹, Zaid Taha^{1

2}, Iris Teo^{1

3}, Siddarth Singh¹, Rameen Jamil¹, Ricardo Marius^{1

2}, Nikolas Martin¹, Taylor Jamieson^{1

2}, Taha Azad^{1

2

4

5}, Jean-Simon Diallo^{1

2}, Carolina S Ilkow^{1

2}, John C Bell^{1

2}

Affiliations

¹ Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
² Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
³ Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
⁴ Faculty of Medicine and Health Sciences, Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada.
⁵ Centre de Recherche du CHUS, Sherbrooke, QC J1H 5N4, Canada.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; nucleocapsid; poly-epitope; spike; t cell; vaccine; vaccinia virus.