02084nas a2200361   4500000000100000000000100001008003900002260001100041100002700052700002400079700001500103700003000118700002000148700002300168700001900191700002600210700002200236700002500258700001900283700001400302700001800316700002000334700001700354700002500371700002200396700001800418700001800436245010500454856006700559300002200626520106100648022001301709       7                             d  c7/20231 aJenna M. Kastenschmidt1 aSuhas Sureshchandra1 aAarti Jain1 aJenny E. Hernandez-Davies1 aRafael De Assis1 aZachary W. Wagoner1 aAndrew M. Sorn1 aMahina Tabassum Mitul1 aAviv I. Benchorin1 aElizabeth Levendosky1 aGurpreet Ahuja1 aQiu Zhong1 aDouglas Trask1 aJacob Boeckmann1 aRie Nakajima1 aAlgimantas Jasinskas1 aNaresha Saligrama1 aD. Huw Davies1 aLisa E. Wagar00aInfluenza vaccine format mediates distinct cellular and antibody responses in human immune organoids  uhttps://linkinghub.elsevier.com/retrieve/pii/S1074761323002765  aS10747613230027653 aHighly 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.  a10747613