Authors
Guangbo Chen, Jing Guo, John Heath, Tyler R Prestwood, Woo Joo Kwon, Ashley R Smith, Tran T Nguyen, Karan R Kathuria, Elsa Sola, AbuBakr Sangare, Vamsee Mallajosyula, Ryan Furuichi Fong, Azam Mohsin, Lei Chen, Oviya Siva, Cindy Padilla, Mingdian Tan, Cornelia L Dekker, Philip Grant, Ying Lu, Harry B Greenberg, William H Robinson, Catherine Blish, Shai S Shen-Orr, Ahmad Salehi, Holden T Maecker, Purvesh Khatri, Paul J Utz, Yueh-Hsiu Chien, Mark M Davis
Published in
Nature immunology. Jun 12, 2026. Epub Jun 12, 2026.
Abstract
Human vaccine responses vary widely, but the determinants remain incompletely defined. Here we analyzed 66 cytokines across four inactivated influenza vaccine (IIV) cohorts over five seasons (n = 581) and identified baseline serum interleukin (IL)-18 and interferon (IFN)-β as correlates of day 28 antibody responses. To test causality, we evaluated 19 cytokines in human tonsil and spleen organoids and found that type I IFNs, IL-21 and IL-12, but not IL-18 or IFNγ, enhanced antibody production. The addition of IFNβ to IIV recapitulated key features of the live-vaccine cytokine program. IL-12 and IL-21 defined a parallel pathway independent of type I IFNs, with IL-12 inducing IL-21 in humans, unlike in mice. Delivery of IL-21 or IFNβ via mRNA lipid nanoparticles in vivo promoted long-lived plasma cell formation. Together, these findings define parallel pathways that regulate vaccine immunity. Our approach unites high-throughput organoid testing and human cohort studies, establishing a human-centric platform to identify adjuvant candidates.
PMID:
42286357
Bibliographic data and abstract were imported from PubMed on 13 Jun 2026.
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