Project 1

PROJECT ABSTRACT - PROJECT 1 The induction of immune memory is the basis of vaccination, which arguably is the single most impactful medical intervention in human history. Nonetheless, vaccines generally have been less effective against respiratory viral infections. Indeed, the protection offered by currently licensed vaccines against the rapidly evolving respiratory viral pathogens influenza and SARS-CoV-2 is limited in breadth and short-lived in duration. These shortcomings have necessitated annual (or more frequent) booster immunizations against these viruses. There is an urgent need to understand the unique immunological challenges faced by these vaccines to be able to enhance their protective capacity and durability. Specifically, key knowledge gaps remain with respect to the clonal and functional dynamics of the germinal center (GC) response over time, and how these dynamics impact the durability, breadth, and ultimately the protective capacity of vaccine induced immune responses. In this Project, we will utilize cohorts of vaccinated adults with unique matched samples from blood, draining lymph nodes, and bone marrow and employ stable isotope labeling of proliferating cells to study at the cellular, molecular, and genetic levels how GC response dynamics impact qualitative and quantitative antibody, B cell, and T cell responses after influenza virus or SARS-CoV-2 vaccination. These innovative studies will provide new information on human immune responses and inform design of new vaccines targeting mutable respiratory pathogens.