Invited Speaker Oral Presentation Lorne Infection and Immunity 2023

Predicting immunogenicity using human tonsil organoids (#8)

Lisa Wagar 1
  1. University of California Irvine, Irvine, CA, United States

Highly effective vaccines elicit specific, robust, and durable adaptive immune responses and ideally stimulate local immune responses at the site of infection to mediate optimal protection. However, it has been challenging to understand and design vaccine candidates with these properties beyond empirical testing in animal models and validation in clinical trials. ​​To make advances in informed vaccine design, it is critical that we understand the cellular dynamics underlying human adaptive immune responses to different antigen formats. Tonsils are considered both lymphoid and mucosal tissues; they are also accessible from otherwise-healthy patients. In this study, we sought to understand how antigen-specific B and T cells are recruited to adaptive immune responses within the mucosal site. Using a human tonsil organoid model, we tracked the dynamics of the adaptive immune response to influenza vaccine and virus modalities. Each antigen format elicited distinct B and T cell responses, including differences in the magnitude, diversity, phenotype, function, and breadth. These differences culminated in striking changes in the corresponding antibody response. We show that a major source of response variability related to antigen format is the ability to recruit naive vs. memory B cells. These findings have important implications for vaccine design and the generation of protective immune responses in the upper respiratory tract.