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Beyond the spike: novel COVID vaccine candidate targets 7 viral proteins for strong immune response


November 2, 2023

Researchers stand on a staircaseResearchers have developed a new COVID vaccine candidate that generates a strong and multipronged immune response against seven different SARS-CoV-2 proteins.
Despite the widespread availability of COVID-19 vaccines in many countries, SARS-CoV-2 continues to spread and make people sick and new variants remain a significant threat.

Researchers at The Ottawa Hospital and the University of Ottawa believe they can counter this threat with a new vaccine candidate dubbed TOH-VAC-2. It generates a strong and multipronged immune response against seven different SARS-CoV-2 proteins, compared to typical COVID-19 vaccines which only target the spike protein.

TOH-VAC-2 uses a replicating vaccinia virus delivery system, which generates a 1,000 fold greater immune response than a non-replicating version in mouse models. It can also be manufactured, stored and transported much more easily than other vaccines, making it an ideal candidate for distribution to lower income countries.

“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 COVID-19 vaccines that provide broader and longer-lasting protection,” said co-senior author Dr. Carolina Ilkow, senior scientist at The Ottawa Hospital, associate professor at the University of Ottawa and a key member of the Canadian Pandemic Preparedness Hub (CP2H). “We believe TOH-VAC-2 could fill this need, while also providing a template for the development of innovative vaccines for other diseases.”

Researchers harnessing expertise on cancer-fighting viruses

The idea to develop a COVID-19 vaccine came from a group of postdoctoral fellows, graduate students and research technicians working with Dr. Ilkow and Dr. John Bell in The Ottawa Hospital’s Cancer Centre. The team normally focuses on developing viruses to fight cancer, but when the pandemic hit, they realized they could quickly adapt their research to develop a vaccine against COVID-19. They also knew they could manufacture large quantities of the vaccine in The Ottawa Hospital’s Biotherapeutics Manufacturing Centre – the only facility of its kind in the country.

A researcher stands in a lab“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 COVID-19 vaccines that provide broader and longer-lasting protection,” said Dr. Carolina Ilkow. “We believe TOH-VAC-2 could fill this need, while also providing a template for the development of innovative vaccines for other diseases.”
TOH-VAC-2 is the second major vaccine candidate developed by the team, after TOH-VAC-1.

“This second vaccine is very effective in training the immune system to target virus-infected cells, in addition to producing antibodies,” explained Dr. Stephen Boulton, lead author on a new paper describing the vaccine. “Importantly, the new vaccine incorporates parts of the virus that don’t generally change over time, so you wouldn’t need a new vaccine every time there’s a new variant.”

Partnership will be key for moving into human clinical trials

The research was initially funded through a Fast Grant in partnership with the Thistledown Foundation and a COVID-19 Emergency Response Fund grant from The Ottawa Hospital Foundation. The team then received additional funding through the Canadian Institutes of Health Research COVID-19 Rapid Research Funding Opportunity. The Canada Foundation for Innovation also provided infrastructure support for the biomanufacturing. Many of the trainees involved in the research were supported by the Canadian Partnership for Research in Immunotherapy Manufacturing Excellence (CanPRIME), with funding from Mitacs and BioCanRx.

The team is continuing to explore partnerships to help move the research into human clinical trials.

Dr. Ilkow and Dr. Bell are key members of the new Canadian Pandemic Preparedness Hub (CP2H). Co-led by the University of Ottawa, in partnership with The Ottawa Hospital, and McMaster University, CP2H is bringing industry, academia and the health care sector together to support the development of made-in-Canada solutions to future pandemics and global health challenges. CP2H is one of the five hubs funded through the integrated Canada Biomedical Research Fund (CBRF) and Biosciences Research Infrastructure Fund (BRIF).

Full reference:  A T Cell-Targeted Multi-Antigen Vaccine Generates Robust Cellular and Humoral Immunity Against SARS-CoV-2 Infection. Molecular Therapy Methods & Clinical Development. Available online 16 September 2023. 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.

The Ottawa Hospital is a leading academic health, research and learning hospital proudly affiliated with the University of Ottawa and supported by The Ottawa Hospital Foundation.