Louis Flamand

Louis Flamand

Virology Pillar 3 Lead

Chair, Executive Committee, Canadian Consortium of Academic Biosafety Level 3 Laboratories (CCABL3)
Professor and Chair, Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Laval University

Denis Leclerc

Denis Leclerc

Virology Pillar 3 Deputy

Professor, Université Laval

Silvia Vidal

Virology Pillar 3 Deputy

Professor, McGill University

Stephen Barr

Stephen Barr

Virology Pillar 3 Deputy

Associate Professor, Western University

Darryl Falzarano

Darryl Falzarano

Pillar 3 Deputy

Scientist, Vaccine and Infectious Diseases Organization

Jennifer Corcoran

Jennifer Corcoran

Virology Pillar 3 Deputy

Associate Professor, University of Calgary

Samira Mubareka

Virology Pillar 3 Deputy

Scientist, Sunnybrook Research Institute

Since its inception, CoVaRR-Net’s Pillar 3 Virology team, under the guidance of Dr. Louis Flamand has made remarkable strides in understanding SARS-CoV-2 biology and developing novel therapeutics and vaccines.

In projects led by Dr. Denis Leclerc, Dr. Flamand says one of the major achievements has been the development of an innovative SARS-CoV-2 vaccine targeting the virus’s nucleocapsid protein.

“The vaccine leverages the virus’s nucleocapsid (N) as the antigen, combined with a nanoparticle containing adjuvant properties that amplify the immune response, specifically targeting the N protein,” explains Dr. Flamand. Therefore, this vaccine differs substantially from the COVID-19 vaccines currently in use in North America. So far, all approved vaccines elicit an antibody response to the spike protein and its receptor binding domain, not the nucleocapsid.

“Through two separate challenge studies, one in collaboration with Dr. Leclerc’s team at Laval University, and another with Dr. Siliva Vidal’s group at McGill University, they’ve demonstrated the vaccine’s remarkable ability to significantly reduce the viral load of the ancestral variant in the lungs of vaccinated animals,” says Dr. Flamand. “Additionally, it has demonstrated a profound impact on reducing levels of IL-6 and TNF-alpha, thereby alleviating inflammation caused by viral infection in the lung tissues.”

Dr. Flamand also points to another prominent member of the Pillar 3 team, Dr. Stephen Barr at Western University, whose network-funded research has focused on developing strategies to combat viral infections, especially SARS-CoV-2. This includes the study of BOLD-100, based on the metal ruthenium, which is being tested for treating advanced gastrointestinal cancer. Dr. Barr’s team also found that this new drug strongly blocks the reproduction of the SARS-CoV-2 virus and its harmful effects in laboratory experiments. They discovered it also worked against other viruses, meaning it could be a good candidate to fight various viral infections, including SARS-CoV-2 and its variants.

Dr. Flamand’s laboratory has made strides in understanding SARS-CoV-2 evolution. “Our results indicate that some mutations were rapidly acquired and maintained, suggesting they provided advantages to the virus. One striking observation was the continued acquisition of the spike protein mutation S371F in Beta and Delta variants, a mutation typically observed only in Omicron variants. This mutation confers immune evasion properties and is what – at least partially – explains why people are still getting infected with SARS-CoV-2, even after vaccines and previous infections,” he explains.

For his part, Dr. Leclerc highlights his team’s research into using nanoparticles in nasal spray vaccines.

“A single intranasal treatment with nanoparticles possessing adjuvant properties has been shown to protect against SARS-CoV-2 infection,” Dr. Leclerc shared. “This nanoparticle-induced immunity protected animals for 3 to 5 days, and there is evidence suggesting that this protection can be extended with repeated treatments. This nanoparticle is expected to induce protection against any respiratory viral disease, as already shown with the influenza A virus.”

Additional research insights include Dr. Silvia Vidal’s contributions that underline the importance of genetic factors and immune responses in COVID-19 severity. Studies comparing different mouse models revealed significant differences in disease outcomes based on genetic background and early immune response, emphasizing the role of early T cell activation in protecting against severe disease.

Dr. Vidal’s analysis of immunosuppressed patients revealed a recurring mutation in the virus’s envelope protein, which inhibits interferon responses, providing insights into how SARS-CoV-2 can evade the immune system. Collaborative efforts are ongoing to develop robust genetic systems for investigating SARS-CoV-2 variants and establishing a cloning-free reverse genetic system for emerging viruses.

Collectively, the findings of Dr. Vidal’s research provide critical insights into the complex interplay between genetic factors and immune responses in COVID-19, highlighting the importance of interdisciplinary research and continued collaboration to address pandemic challenges.

Looking ahead, Dr. Flamand outlined the primary goals for Pillar 3 in the months ahead. “The priorities include finalizing ongoing research projects. For instance, Dr. Leclerc’s vaccination and challenge protocol aims to assess the efficacy of the vaccine his team developed against the Omicron XBB.1.5 variant,” says Dr. Flamand.

Dr. Flamand’s work will focus on generating recombinant SARS-CoV-2 to define why certain variants of concern are much more virulent than others.  “We have developed an efficient method to generate recombinant SARS-CoV-2, enabling us to identify which part of the genome contains virulence genes.  Through loss of function, attenuated viruses will be generated to identify virulence factors,” he explained.

Despite these incredible achievements by Pillar 3, Dr. Flamand notes there have also been challenges, particularly the issue of short-term funding.

“We have put immense efforts into building the network and mobilizing Canada’s brightest scientists to work together towards pandemic preparedness. As the network has reached maturity, funding is terminated, resulting in the dismantling of one of the most successful networks in Canada. Without a long-term vision and sustained investments, Canada will be a follower rather than a leader in the fight against pathogens with pandemic potential,” he stressed.

“Perhaps the greatest success obtained through CoVaRR-Net is the establishment of a functional network of scientists that can be rapidly mobilized to unite their efforts in response to a crisis. I am confident that I can call up pretty much anyone in the field for advice or access to a pathogen and receive a positive response within a short delay. This constitutes one of the greatest achievements made,” Flamand concluded.