Find Paper, Faster
Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune response [Immunology and Inflammation]
Proceedings of the National Academy of Sciences of the United States of America  (IF11.205),  Pub Date : 2021-09-28, DOI: 10.1073/pnas.2103651118
Laura Roßmann, Katrin Bagola, Tharshana Stephen, Anna-Lisa Gerards, Bianca Walber, Anja Ullrich, Stefan Schülke, Christel Kamp, Ingo Spreitzer, Milena Hasan, Brigitte David-Watine, Spencer L. Shorte, Max Bastian, Ger van Zandbergen

The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast to commonly used adjuvants, such as aluminum hydroxide, Toll-like receptor (TLR) agonists induced robust phenotypic and functional DC maturation. In a DC-lymphocyte coculture system, we investigated the ensuing immune reactions. While monophosphoryl lipid A synthetic, a TLR4 ligand, induced checkpoint inhibitors indicative for immune exhaustion, the TLR7/8 agonist Resiquimod (R848) induced prominent type-1 interferon and interleukin 6 responses and robust CTL, B-cell, and NK-cell proliferation, which is particularly suited for antiviral immune responses. The recently licensed COVID-19 vaccines, BNT162b and mRNA-1273, are both based on single-stranded RNA. Indeed, we could confirm that the cytokine profile induced by lipid-complexed RNA was almost identical to the pattern induced by R848. Although this awaits further investigation, our results suggest that their efficacy involves the highly efficient antiviral response pattern stimulated by the RNAs’ TLR7/8 activation.