Mechanisms of Immune Protection Against Respiratory Viruses

PROJECT ABSTRACT - OVERALL The SARS-CoV-2 pandemic highlighted the urgent need for better understanding of the mechanisms controlling broadly protective immune responses to rapidly evolving viral pathogens and generating vaccine candidates able to elicit such responses. The Washington University Cooperative Center on Human Immunology (WashU- CCHI) application (Mechanisms of Immune Protection Against Respiratory Viruses) proposes a comprehensive research plan towards two main goals: (a) defining the mechanisms of germinal center persistence after vaccination in humans and how germinal center dynamics impact engagement of de novo B cells and generation of robust CD4+ T cell, long-lived memory B cell, and bone marrow plasma cell responses (Project 1); (b) determining the functional caliber of systemic and mucosal immune responses to vaccines and infection and how these impact durability, breadth, and protection (Project 2). Three Cores will synergize with the two research projects to support the successful completion of the research aims. The Administrative Core (Core A) will manage the consortium, coordinate cross-project activities, and create the structure and environment needed to accomplish WashU-CCHI's goals. The Clinical Core (Core B) will provide the clinical and statistical expertise to support the design and conduct of the human subjects' research studies conducted under Projects 1 and 2. The Proteomics Core (Core C) will capitalize on an array of unique technologies for the interrogation of the circulating antibody protein and B cell repertoires in samples collected under Projects 1 and 2. The integrated and synergistic activities across these Projects and Cores will drive the successful completion of the WashU-CCHI's ambitious research agenda, enabling achievement of our long-term goals of providing key insights on human immune responses and informing evaluation of new mucosal vaccines targeting the human respiratory tract against existing and emerging respiratory viral pathogens.