The world may be facing an impending crisis and immediate threat from an uncontrolled influenza outbreak. An influenza pandemic has greater potential to cause large numbers of deaths/illnesses over a shorter time period than virtually any other natural health threat. Antibody-mediated influenza vaccines are extremely strain- specific due to highly variable hemagglutinin (HA) and neuraminidase (NA) antigens. Moreover, influenza vaccines are not effective in the elderly population that is most at risk for developing lethal infection. For this reason, there is an urgent need to develop vaccines that control multiple strains over many years including in the elderly. The clearest means of preventing or minimizing the global catastrophe that will result from widespread infectio of a susceptible human population with a new influenza pandemic strain is prophylactic vaccination aimed at inducing broadly reactive, universal immune responses against a range of viral isolates and subtypes. The goal of this project is to demonstrate that effector memory T cell (TEM) induced by CMV- vectors carrying conserved flu antigens will protect against deadly forms of influenza virus. To this end we will design new Rhesus CMV vaccine vectors expressing conserved influenza internal proteins and test the ability of the novel T cells induced by these vaccines to protect against highly pathogenic avian influenza. Successful completion of these studies would lay the foundations for a novel approach to develop a universal influenza vaccine.
The development of a universal influenza vaccine remains one of the top global health priorities and novel approaches are urgently needed. Cytomegalovirus (CMV)-induced T cells target unique epitopes and these novel T cells have shown enhanced ability to contain mucosal pathogens. Therefore, we propose here to develop a CMV-based T cell vaccine to protect against influenza.