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[0] Ertl, Hildegund [1] An Improved Influenza A Vaccine for Rapid Protection of the Elderly [2] The Wistar Institute [3] NO1-AI-50030* [4] 
The goal of this application is to conduct pre-clinical studies for a vaccine designed to provide protection to the elderly in the event of a bioterror attack with influenza A virus. Protection against most viral infections, including those with influenza A virus can most readily be achieved by vaccines that elicit serotype-specific neutralizing antibodies. This may not be attainable in the event of a bioterror attack, as generation of such a vaccine could not be achieved in a timely fashion. CD8+ T cells directed against more conserved viral sequences can lower the impact of viral infections and it is the goal of this application to develop a CD8+ T cell-inducing vaccine suitable for use in the elderly that provides broad protection against different types of Influenza A virus. Adaptive immune responses of the elderly are commonly impaired in part due to physiological cell senescence and in part due to a loss of equilibrium between activating and inhibitory pathways following chronic antigenic stress. The latter are expected to be amenable to pharmacological adjustment as will be addressed by this application. Suitable cohorts of human subjects will be identified and blood samples collected for analyses. In addition, potential targets or regulatory circuits will be identified in mice and human samples that may be exploited in increase the efficacy of the influenza vaccine vector in the elderly. The vaccine generated will be based on an E1-deleted adenoviral vector of the simian serotype 68 (AdC68) expressing internal proteins of Influenza A virus and shall be supplemented with suitable monoclonal antibody preparations to improve its performance in the elderly by circumventing negative co-stimulation and/or increasing positive co-stimulation.
ImmPort: Immunology Database and Analysis Portal
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