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Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids

2023; Cell Press; Volume: 56; Issue: 8 Linguagem: Inglês

10.1016/j.immuni.2023.06.019

1097-4180

Jenna M. Kastenschmidt, Suhas Sureshchandra, Aarti Jain, Jenny E. Hernandez‐Davies, Rafael de Assis, Zachary W. Wagoner, Andrew M. Sorn, Mahina Tabassum Mitul, Aviv I. Benchorin, Elizabeth Levendosky, Gurpreet S. Ahuja, Qiu Zhong, Douglas K. Trask, Jacob Boeckmann, Rie Nakajima, Algimantas Jasinskas, Naresha Saligrama, D. Huw Davies, Lisa E. Wagar,

Immunotherapy and Immune Responses

Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the cellular dynamics underlying responses to different antigen formats. Here, we sought to understand how antigen-specific B and T cells were activated and participated in adaptive immune responses within the mucosal site. Using a human tonsil organoid model, we tracked the differentiation and kinetics of the adaptive immune response to influenza vaccine and virus modalities. Each antigen format elicited distinct B and T cell responses, including differences in their magnitude, diversity, phenotype, function, and breadth. These differences culminated in substantial changes in the corresponding antibody response. A major source of antigen format-related variability was the ability to recruit naive vs. memory B and T cells to the response. These findings have important implications for vaccine design and the generation of protective immune responses in the upper respiratory tract.