The objective of this contract program is to support improvements in the immunogenicity and durability of seasonal influenza vaccines, and the development of innovative influenza vaccine approaches that provide robust, durable, broadly protective mucosal and systemic anti-influenza immunity (?universal influenza vaccines?). This will be done through NIAID-supported Collaborative Influenza Vaccine Innovation Centers (CIVICs). Each CIVIC will support iterative vaccine design based on detailed immunologic assessment of influenza vaccine candidates through pre-clinical animal studies, early phase clinical trials and healthy volunteer human challenge studies to advance the most promising vaccine candidates into Phase I/II clinical trials. University of Georgia?s Center for Influenza Vaccine Research in High Risk Populations (CIVR-HRP) builds upon many years of collaborative work by the primary investigators, and proposes a comprehensive research program centering on identifying broadly protective influenza vaccines for all populations with a focus on our most vulnerable populations. The program couples the skills of established and junior investigators, and combines our historical program strengths in vaccine development, virology, immunology, animal models, validated assay and reagent development, systems biology, bioinformatics and structural biology, and their extensive and world-class facilities and resources including St Jude Children?s Research Hospital (SJCRH) GMP facility with novel and innovative study designs such as comprehensive assessment of immune and omics responses to vaccination, novel platforms and adjuvants, and exploration of immune correlates of protective immunity in high-risk populations.