Picrasidine S Induces cGAS‐Mediated Cellular Immune Response as a Novel Vaccine Adjuvant

• DOI: 10.1002/advs.202310108
• Publication Date: 2024-06-20T13:49:58Z
• Authors: Xiaofan Ding; Mengxue Sun; Fusheng Guo; Xinmin Qian; Haoyu Yuan; Wenjiao Lou; Qixuan Wang; Xiaoguang Lei; Wenwen Zeng
• Keywords: 0303 health sciences; 03 medical and health sciences; adjuvant; cancer prevention; Science; Q; type I interferon; cellular immune response; cGAS; Research Article

AbstractNew adjuvants that trigger cellular immune responses are urgently needed for the effective development of cancer and virus vaccines. Motivated by recent discoveries that show activation of type I interferon (IFN‐I) signaling boosts T cell immunity, this study proposes that targeting this pathway can be a strategic approach to identify novel vaccine adjuvants. Consequently, a comprehensive chemical screening of 6,800 small molecules is performed, which results in the discovery of the natural compound picrasidine S (PS) as an IFN‐I inducer. Further analysis reveals that PS acts as a powerful adjuvant, significantly enhancing both humoral and cellular immune responses. At the molecular level, PS initiates the activation of the cGAS‐IFN‐I pathway, leading to an enhanced T cell response. PS vaccination notably increases the population of CD8+ central memory (TCM)‐like cells and boosts the CD8+ T cell‐mediated anti‐tumor immune response. Thus, this study identifies PS as a promising candidate for developing vaccine adjuvants in cancer prevention.