Grant: Operating Grant

Influenza virus is one of the top ten leading causes of death in Canada, and remains one of the gravest threats to global public health due to its propensity to cause pandemics. To combat seasonal influenza epidemics, massive annual vaccination programs are carried out at tremendous expense to the healthcare system. The ability of influenza virus to cause seasonal epidemics is conferred by its capacity to rapidly evolve in order to escape pre-existing immunity. This in turn necessitates that influenza virus vaccines be reformulated on a nearly annual basis. Frequently, the strains of influenza virus that actually circulate do not perfectly resemble the strains included in the vaccine. Due to the exquisitely strain-specific immunity that current vaccines elicit, vaccine efficacy can suffer substantially when imperfect matches occur. More importantly, current vaccines offer little to no protection against the emergence of a novel influenza virus pandemic. Therefore, there is a tremendous need to develop new influenza virus vaccines capable of inducing broad and long-lasting protection. The recent discovery of broadly-neutralizing antibodies that bind to the stalk domain of hemagglutinin has raised the hope that development of a "universal" influenza virus vaccine may be within reach. While many studies have addressed how these antibodies function in isolation, little is known about the way that broadly-neutralizing antibodies are generated and function in the context of the polyclonal responses that are naturally elicited by vaccination and infection. Our studies will define the mechanisms that govern the generation and function of broadly-neutralizing antibodies in the context of the polyclonal response to infection and vaccination. The knowledge gained from these studies will be used to advance the development of "universal" influenza virus vaccines and therapeutics which have the potential to substantially reduce the global burden of influenza-related illnesses