CoVaRR-Net’s Pillar 1 Team on Collaboration and Breaking New Ground in the Fight Against COVID-19

The fight against COVID-19 has been a crash course in adapting quickly to a rapidly evolving virus. CoVaRR-Net’s Pillar 1 Immunology & Vaccine Protection team has been on the front line of that fight. Mandated to investigate the human immune system’s response to emerging variants and assess the effectiveness of vaccines against them, its work has left an indelible mark on pandemic preparedness and vaccine research.

Among Pillar 1’s achievements has been building the capacity to answer critical questions about immunity. The team established a cohort of healthy adult vaccine recipients, representing various vaccine combinations used across Canada.

“We created a robust foundation for studying vaccine-induced immunity,” says Dr. Ciriaco Piccirillo, Pillar 1 Co-Lead and Professor at McGill University. “These samples were shared with collaborators, leading to a deeper understanding of how vaccines stimulate immune responses and provided insights into optimizing future vaccination strategies. It’s been of incredible value.”

Pillar 1’s research led to numerous important findings during the pandemic. First, it was shown that vaccination leads to systemic and limited/transient mucosal antibody responses. Additionally, a combination of two vaccine doses followed by an Omicron breakthrough infection was found to heighten both systemic and mucosal immune responses more effectively than three vaccine doses. The research also demonstrated that vaccination with wild-type SARS-CoV-2 spike-encoding vaccines provides limited protection against infection or reinfection by Omicron variants. Finally, it revealed that selective pressure for T cell immune evasion in spike regions occurs during transmission between hosts. The team also characterized the antibody and memory B cell response to nine variants.

Pillar 1 also evaluated immunity in several populations, finding the following: A third COVID-19 mRNA vaccine dose or a breakthrough infection significantly boosts T cell immunity to comparable levels in older adults, similar to younger adults after their second dose. People living with HIV who are receiving anti-retroviral therapy showed similar levels of immunity after three mRNA vaccine doses and benefited from a fourth dose. In children with primary immunodeficiencies, a third vaccine dose resulted in a humoral response similar to that of healthy children after two doses. However, children with secondary immunodeficiencies did not appear to develop neutralizing antibodies, indicating the need for novel vaccination strategies for immunocompromised children. Finally, antibody responses to vaccination showed age- and sex-related differences.

Several Pillar 1 project breakthroughs were the result of collaborations within and across pillars, something Dr. Jennifer Gommerman, Pillar 1 Co-Lead and Professor at the University of Toronto, says has been vital since the start of the pandemic. “CoVaRR-Net has been really useful and essential in bringing people together, brainstorming ideas, and establishing models to get preliminary data,” she notes. “It’s those shoulders that we stand on that allow us to look forward.”

That collaboration between pillars was evident with the development of a computational pipeline to evaluate and predict how mutations in viral variants may evade antibodies. A joint effort between Pillar 1 and Pillar 6/CAMEO (CoVaRR-Net’s Computational Analysis, Modelling and Evolutionary Outcomes team), suggested that cross-reactivity from seasonal coronaviruses could influence antibody responses to SARS-CoV-2-specific epitopes during transmission, providing critical insights into immune dynamics and viral evolution. “These findings have the potential to shape public health strategies and bolster pandemic preparedness,” says Dr. Piccirillo. “It’s yet another way our studies can contribute to ongoing public health efforts to optimize vaccination regimens for vulnerable populations.”

The challenges of conducting research during a pandemic underscored the need for adaptability. Dr. Gommerman says delays in receiving supplies, vaccine shortages, and the evolving nature of the virus required researchers to adapt quickly and often. “We had to pivot the research as the landscape evolved,” she explains. “What was once our big, exciting question sometimes had to change because suddenly, one group had a breakthrough. How do we do the same experiment? The answer was we don’t and instead we must pivot.”

Pillar 1’s work has played a key role in shaping the future of vaccine strategies in Canada. From research on adaptive immune responses in adults and children to inform vaccination schedules and delivery methods for vulnerable groups, exploring mucosal immunity, paving the way for innovative vaccine delivery strategies, to insights into antibody and cell-mediated immunity that’s sparked new research into other diseases beyond COVID-19, Pillar 1 continues to expand the impact of its work.

“All of these findings are instrumental in developing more effective immunization approaches and advancing Canada’s pandemic preparedness,” says Gommerman. “It will help ensure that future immunization plans are effective and inclusive.”

With federal COVID-19 funding winding down for CoVaRR-Net, Pillar 1’s legacy is one of scientific rigour, adaptability, and collaboration.  “The work underscores that science, at its best, is a team effort,” says Dr. Piccirillo. “By working collaboratively, we’ve ensured that Pillar 1’s contributions will resonate far beyond the pandemic, guiding us towards a healthier and more prepared future.”

Dr. Piccirillo is also grateful to have had the opportunity to work under the CoVaRR-Net banner. “There was a natural willingness to share know-how, skills, and resources to achieve our goals,” he says. “It was a support group throughout the pandemic, with people talking to and encouraging each other. We can’t dismiss the importance of that.”