INSIS study unveils secrets of rare vaccine events, shaping future immunizations

A University of Alberta professor is co-leading a new international vaccine safety network to examine why some people who received a COVID-19 vaccine experienced very rare adverse events associated with the vaccine.

The International Network of Special Immunization Services (INSIS), based at the U of A, is a consortium of academic medical centers around the world coming together to study very rare adverse events after vaccination. An adverse reaction is considered very rare when it affects less than .001 per cent of the population.

"The bar for safety with vaccines is very high because we're giving them to healthy people to prevent them from getting sick," says U of A pediatric infectious disease professor Dr. Karina Top, who alongside Dr. Robert T. Chen, scientific director of the Brighton Collaboration -; a leading non-profit vaccine safety organization -; is co-leading INSIS. "We don't want these events to occur, and we want to understand why, so we can prevent them in the future."

INSIS is receiving up to US$15.3 million over four years from the Coalition for Epidemic Preparedness Innovations (CEPI) to study why these very rare adverse events happen and who is most at risk. The network aims to help manufacturers develop new vaccines that will be even safer.

Vaccines have helped to eradicate deadly diseases such as smallpox, they save two-to-three million children a year, and they even help to combat certain types of cancer such as cervical and throat cancers, which are caused by HPV. The impact of COVID-19 vaccines has been even more striking. In the first year of their rollout during the pandemic, vaccines saved 20 million lives.

Very rare adverse events associated with immunizations tend to be detected after vaccines are rolled out at a population level. Clinical trials typically include a relatively small number of participants, which may not fully represent the diverse population that will receive a vaccine after its approval. When the vaccine is rolled out to millions of people, a broader range of individuals with varying health conditions and genetic backgrounds may receive a vaccine. This increased sample size allows for detection of very rare adverse events that might occur.

Cutting-edge safety science

The INSIS team will use cutting-edge techniques to measure the types of cells and molecules in human blood samples to identify how a vaccine may trigger an adverse event. The INSIS team will compile unprecedented amounts of data from around the world to compare information about people who experienced very rare adverse events and those who did not.

The ultimate goal of this project will be to enhance the safety assessment of vaccine candidates developed to combat emerging infectious threats before emergency authorization. This will be critical for achieving the 100 Days Mission, which aims to compress vaccine development against such pathogenic threats with pandemic potential to within just 100 days of their identification.

Compressing vaccine development against emerging pathogens down to 100 days will be critical to combatting future pandemic threats. Data from INSIS will help to inform health authorities on the most appropriate type of vaccine that should be used in specific outbreak settings and populations. If we can identify risk factors and identify causal mechanisms for potential serious adverse events ahead of time, immunization campaigns can be adapted to mitigate such risks in those who are potentially vulnerable to harm, contributing to increased levels of public confidence in vaccines and enabling the development of even safer vaccines."

Jakob Cramer, director of clinical development at CEPI

This global study brings together researchers from the University of Alberta, B.C. Children's Hospital Research Institute and institutions in at least seven countries, including the Precision Vaccines Program at Boston Children's Hospital, Mayo Clinic's Vaccine Research Group, the Vanderbilt Vaccine Research Program at Vanderbilt University Medical Centre, Murdoch Children's Research Institute in Australia, the Global Vaccine Data Network co-ordinated from New Zealand, Ospedale Pediatrico Bambino Gesù in Italy, Global Healthcare Consulting co-ordinated from India, and the African Leadership in Vaccinology Expertise (Wits-ALIVE).