Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells 3384

Abstract Description Squalene-based emulsion (SE) adjuvants like MF59 and AS03 are used in protein subunit vaccines against influenza virus and SARS-CoV-2. We demonstrate the critical role of uric acid (UA), a damage-associated molecular pattern (DAMP), in triggering immunogenicity by SE adjuvants. In mice, SE adjuvants elevated DAMP levels in draining lymph nodes. Strikingly, UA perturbation reduced the vaccine-induced innate immunity, to subsequently impair antibody and T cell responses. In vivo treatment with UA crystals elicited partial adjuvant effects. In vitro stimulation with UA crystals augmented the activation of dendritic cells (DCs) and B cells and altered multiple pathways in these cells, including inflammation and antigen presentation in DCs and cell proliferation in B cells. In an influenza vaccine model, UA contributed to protection against influenza viral infection. These results demonstrate the importance of DAMPs, specifically the versatile role of UA in the immunogenicity of SE adjuvants, by regulating DCs and B cells. Funding Sources Supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT; grant number NRF-2021R1C1C1012962 and RS-2024-00398073). Topic Categories Vaccines and Immunotherapy (VAC)