CoVaRR-Net Researchers

Louis Flamand, Université Laval, Pillar 2 and Project Lead

Steve Barr, Western University, Pillar 2 Deputy
Jenn Corcoran, University of Calgary, Pillar 2 Deputy
Darryl Falzarano, Vaccine and Infectious Disease Organization (VIDO), Pillar 2 Deputy
Denis Leclerc, Université Laval, Pillar 2 Deputy
Silvia Vidal, McGill University, Pillar 2 Deputy
Jenn Gommerman, University of Toronto, Pillar 1 Lead
Anne-Claude Gingras, Sinai Health Systems, Pillar 3 Lead
Ioannis Ragoussis, McGill University, Pillar 4 Lead
Jesse Shapiro, McGill University, Pillar 5 Lead
Marc-André Langlois, University of Ottawa, Executive Director

Lay Summary

Despite a wealth of information, much remains to be learned regarding the pathogenesis (the process by which a disease or disorder develops) of SARS-CoV-2 and its variants. The way in which SARS-CoV-2 develops into COVID-19 is complex, misunderstood, and includes multiple factors. It is believed that it is, in part, likely the result of exaggerated inflammation and coagulation responses. A better understanding of how the virus develops into the disease would aid in vaccine optimization. Further improving vaccines is important as the current vaccines may be less effective in controlling variants of concern (VOCs), spreading rapidly around the world, including here in Canada. Better understanding how the virus develops and strengthens will also help Canadian decision-makers respond rapidly to variants.

Certain mutations found in the variants, such as D614G and N501Y in the Spike gene, increase the virus’s transmissibility and virulence. Most studies have focused on Spike mutations because they may influence the immune protection generated by current vaccines. However, VOCs contain mutations in many other genes, and whether these mutations affect the development of immunity and/or the virulence of the virus is unknown.

This project will focus on the Gamma and Delta variants (see table), given that they appear to be the most problematic at this time. The project has three objectives:

1) Fitness, pathogenesis and immune escape of in vitro and in vivo evolved VOCs. This portion of the project will use reverse genetics to help a) understand the impact of certain mutations on the growth and fitness of VOCs b) anticipate how the virus will evolve and strengthen in Canada by creating a rapidly mutating version of the virus to study an accelerated evolutionary process of SARS-CoV-2. The evolution of the Delta VOC will also be studied in mice.

2) Animal models to study SARS-CoV-2 pathogenesis and correlates of protection. This part of the project will investigate the connection between host genetic factors, co-morbidities, such as hypertension, and severe COVID-19. Researchers will compare the ability of vaccines and therapeutics to protect against severe COVID-19 and endeavour to draw connections between symptoms and outcome.

3) Antibody maturation and vaccine-induced protection against VOCs. This segment of the project will study the effects of vaccines on small animals with the Alpha and Delta variants. Researchers will investigate the entire antibody response to determine whether vaccine-induced immunity increases over time and if it protects against other variants.

Budget

CoVaRR-Net: $200,000 cash contribution

Table of non-synonymous mutations in each gene of the Gamma and Delta VOCs