Mechanistic investigation of vaccine immunogenicity

Adenovirus vector and mRNA vaccines have proven their real-world efficacy as rapidly deployable modular vaccine platforms. However, major differences exist between the two systems, particularly with respect to immunogenicity where mRNA vaccines induce markedly stronger antibody responses. The reason for these differences remains unknown. Furthermore, my preliminary data has revealed important qualitative differences in the B cell responses induced by these two vaccines, particularly around the role of the germinal center response. Thus, there are key quantitative and qualitative differences in the B cell immunity induced by these vectors, but a mechanistic understanding of the cause is lacking. My project will address this major gap in knowledge using a combination of human and mouse immunology techniques involving bioinformatic and experimental approaches. Specifically, my project will (1) define the dynamics of the B cell responses induced by these vaccine technologies, (2) identify critical regulators of these B cell responses, and (3) define how T follicular helper cells are regulated and regulate the subsequent B cell response. Through synthesis of these data, this project will enhance our fundamental knowledge of how these vaccines induce B cell immunity and allow for rational improvements in their design and deployment.