Aging is accompanied by a decline in immune responsiveness that renders older adults highly susceptible to infectious diseases, and immunization vs. vaccine preventable illness such as influenza is less effective in seniors. A recently identified, vaccine-inducible branch of immunity, Th17 immunity appears to be well preserved, perhaps even favored in the immune system of older adult mice. We have preliminary data that both old T cells and old dendritic cells favor a Th17 immune response, and that, on the whole animal level, Th17 immune responses are favored in older animals when compared to young animals. In this proposal, we suggest using the Th17 immune response as a platform for vaccine development in older adult mice and evaluating the effect of Th17 immunity on host defense vs. influenza challenge. We will use two different vaccines to determine which best induces Th17 immunity. One is based on using irradiated Brucella abortus as a vector to carry influenza proteins. The other uses cytokine-coated, inactivated influenza virus to skew the Th response in a specific direction. The capacity of each vaccine platform to induce Th17 immunity and protect from typically fatal influenza virus challenge will be evaluated across the adult lifespan (2 mos to 18 mos). Once the most effective vaccine is established, additional experiments will investigate the role of Th17 in host defenses in both naive and immunized mice. Further, since induction of one Th type (e.g. Th1) inhibits the development of other Th types (e.g. Th17), the influence of Th17 immune induction on Th1 and Th2 immune responses will be determined. The longer-term goal of these studies is to test the feasibility of using a Th17- based vaccine platform in humans. PUBLIC HEALTH RELEVANCE: Older adults are highly susceptible to infectious diseases, and immunization against influenza and other vaccine preventable illnesses are less effective in seniors because host defenses wane with age. In this proposal, we will use a novel vaccine strategy to induce Th17 immunity, a newly discovered type of immunity that appears to be preserved into old age, to try to protect old adult mice from influenza infection. The longer- term goal of these studies is to test the feasibility of using a Th17-based vaccine platform in humans.

R21AG033825

2009-06-01

2012-05-31