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ACS Nano

ACS Nano

IF: 15.8
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Tamibarotene-Loaded Nanoemulsion Incorporating Toll-like Receptor 2/6 Agonist as an Intramuscular Adjuvant System Enhances Gastrointestinal Mucosal Immunity

Published:16 May 2025 DOI: 10.1021/acsnano.5c00563
Yan Deng,Hao Cheng,Ji Zhu,Yue Jiang,Hongwu Sun,Guocheng Li,Jing Wei,Ruoyi Xue,Rang Feng,Jingwen Cao,Wenkang Yu,Yalan Wang,Mingqi Xu,Quanming Zou,Haibo Li

Abstract

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 Pam2CSK4. 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 Pam2CSK4 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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
LMT-28 1239600-18-0 C17H29NO4 39 suppliers $36.00-$850.00
LMT-28 1239600-18-0 C17H29NO4 39 suppliers $36.00-$850.00
LMT-28 1239600-18-0 C17H29NO4 39 suppliers $36.00-$850.00
LMT-28 1239600-18-0 C17H29NO4 39 suppliers $36.00-$850.00

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