Toddlers have limited mucosal protection against Live Attenuated Influenza Virus in human tonsil organoids.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B906
Abstract ID: 4735

Presenting Author:
Meng Sun , postoctoral researcher at Stanford Univ. Sch. of Med.

Abstract:

Children require separate clinical trials to vaccination and other treatments, because we know little about how their immune systems differ from adults. Notably, we developed a high-resolution in-vitro model of human immunity using tonsil organoids. These organoids have demonstrated a remarkable ability to generate specific antibody and T-cell responses to vaccines across a broad age spectrum (2-70 years old). This provides a unique opportunity to investigate the variations to vaccination between children and adults. To study the systemic cellular response to live attenuated influenza virus in human tonsil organoids, we used scRNA-seq via the BD Rhapsody platform, and validated by flow cytometry, ELISA and Luminex assays. Our data showed marked differences between toddlers (2-4 years) and adults (19-39 years). Compared to adults, toddlers exhibited lower levels of flu-specific IgA, IgG antibodies and activated cytotoxic CD8 T cells. Additionally, toddlers displayed a less comprehensive cytokines that help promote class-switched antibody production. Our data also indicated a metabolic transition within germinal centers from oxidative phosphorylation to glycolysis, as individuals progress from early childhood to adulthood. Our study can offer valuable insights to aid vaccine design and administration practices. It may also identify vulnerabilities in children's immune systems with implications for improving therapeutic treatments for infectious diseases.