Grant: Catalyst Grant: Pandemic Outbreak Research Response

An overriding importance of host factors in the outcome of pandemic influenza infection becomes evident by survival of over 90% of individuals infected with the 1918 pandemic H1N1 virus. However, the nature of immune responses or genetic factors that trigger or prevent severe respiratory illness (SRI) and death following pandemic influenza infection in humans are not yet identified. The 2009 H1N1 influenza pandemic is characterized by relatively mild clinical outcomes in a majority of individuals. For reasons not yet understood, the infection in a segment of population, in particular aboriginals, pregnant women, obese individuals and some adults less than 50 years of age, has led to SRI, necessitating hospitalization. To gain insights into the mechanism leading to SRI in humans and the immunological and genetic factors that trigger or prevent SRI, we seize this opportunity to undertake a multicenter retrospective and prospective investigation that focuses on broad objectives addressed under following highly interactive modules: We will study the (i) mechanism and control of SRI in humans after influenza A infection, (ii) The impact of cytotoxic T cell (CTL) memory and Th1/Th2 predominance in escaping or developing SRI, (iii) study the systems biology of H1N1 and development of SRI, (iv) host genetic factors associated with SRI and (v) long term outcome of SRI patients surviving respiratory failure. The proposed collaborative research program is highly significant because we will utilize Canadian expertise to increase investment in influenza research, while promoting Canada as a leader for multidisciplinary training, technology advancement and knowledge translation. With this research infrastructure in place, we will be ideally positioned to contribute to reduc