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

Molecular Therapy: Methods & Clinical Development (Dec 2023)

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

Affiliations

Stephen Boulton: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Corresponding author: Stephen Boulton, PhD, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Joanna Poutou: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Rida Gill: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Nouf Alluqmani: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Xiaohong He: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Ragunath Singaravelu: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Mathieu J.F. Crupi: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Julia Petryk: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Bradley Austin: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Leonard Angka: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Zaid Taha: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Iris Teo: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Siddarth Singh: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Rameen Jamil: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Ricardo Marius: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Nikolas Martin: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Taylor Jamieson: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Taha Azad: 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
Jean-Simon Diallo: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Carolina S. Ilkow: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Corresponding author: Carolina S. Ilkow, PhD, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
John C. Bell: Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Corresponding author: John C. Bell, PhD, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.

Journal volume & issue: Vol. 31
p. 101110

Abstract

Read online

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.

Published in Molecular Therapy: Methods & Clinical Development

ISSN: 2329-0501 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Biology (General): Genetics; Science: Biology (General): Cytology
Website: http://www.cell.com/molecular-therapy-family/methods/latest-content

About the journal

Abstract

Keywords