Tamibarotene-Loaded Nanoemulsion Incorporating Toll-like Receptor 2/6 Agonist as an Intramuscular Adjuvant System Enhances Gastrointestinal Mucosal Immunity

作者：Yan Deng, Hao Cheng, Ji Zhu, Yue Jiang, Hongwu Sun, Guocheng Li, Jing Wei, Ruo‐Yi Xue, Rang Feng, Jingwen Cao, Wenjing Yu, Yalan Wang, Mingqi Xu, Quanming Zou, Haibo Li · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.5c00563 · 被引用次数：5 · 研究领域：Viral gastroenteritis research and epidemiology、RNA Interference and Gene Delivery、Immune Cell Function and Interaction

Parenteral subunit vaccines typically elicit systemic humoral immune responses but often struggle to induce mucosal immunity. Herein, we developed a promising adjuvant system, TB/P2C-NE, a tamibarotene-loaded nanoemulsion incorporating the TLR2/6 agonist Pam 2 CSK 4 . Upon intramuscular vaccination, TB/P2C-NE promoted antigen-specific mucosal immune responses in the gastrointestinal tract, accompanied by systemic humoral and cellular response. Mechanistically, tamibarotene upregulated the intestinal homing molecule CCR9 on lymphocytes through dendritic cell modulation, while Pam 2 CSK 4 increased IL-6 secretion at the injection sites, further amplifying CCR9 expression and lymphocyte activation and leading to enhanced lymphocyte homing to the intestinal mucosa and a subsequent boost in mucosal immunity. Notably, TB/P2C-NE induced long-term gastrointestinal mucosal responses, maintaining elevated sIgA levels for up to three months post-immunization, and also induced gastrointestinal mucosal immunity in combination with a polysaccharide conjugate antigen. Immunization with recombinant intimin using TB/P2C-NE as the adjuvant resulted in a robust protective effect against the EHEC O157:H7 challenge. In summary, TB/P2C-NE offers an adjuvant strategy potentially accelerating the development of vaccines targeting gastrointestinal infections.