He Penghui, He Chunting, Guo Rong, Ou Yangsen, Chang Yu, Xie Zhiqiang, Tang Xue, Xu Yanhua, Zhao Yuanhao, Wang Hairui, Guo Zhaofei, Bai Shuting, Chen Zhengjun, Fan Fan, Du Guangsheng, Sun Xun
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
J Control Release. 2025 Jun 10;382:113740. doi: 10.1016/j.jconrel.2025.113740. Epub 2025 Apr 16.
Mucosal vaccines are considered an ideal choice for combating mucosal pathogens due to their ability to neutralize pathogens at the first line of defense. However, the development of mucosal subunit vaccines is constricted by rigorous challenges, such as low immunogenicity, poor antigen delivery efficiency, and mucosal tolerance. Here, a buccal microneedle patch incorporated with engineered nanoparticles loaded with urease B subunit (rUreB) was developed to overcome the above challenges. Specifically, an engineered nanocarrier was developed to protect the antigen and modulate its release profile. Then, the nanoparticles were enriched to form microneedle tips with superior mechanical and waterproof properties, allowing effective penetration of the buccal mucosa and resistance to salivary washout. Besides, the microneedles demonstrated an S-curve antigen release pattern which was crucial for the recruitment of antigen presenting cells (APCs) and the downregulation of mucosal tolerogenic DCs and Treg cells. The buccal microneedle vaccine without any immune stimulators induced potent systemic and mucosal immune responses, resulting in superior protection of mice from the oral challenge of Helicobacter pylori. These results suggested that the rationally designed buccal microneedle vaccine can effectively overcome mucosal delivery barriers and mucosal tolerance, providing a promising alternative strategy for mucosal vaccination of subunit antigens.
黏膜疫苗因其能够在第一道防线中和病原体而被认为是对抗黏膜病原体的理想选择。然而，黏膜亚单位疫苗的开发受到严格挑战的限制，如免疫原性低、抗原递送效率差和黏膜耐受性。在此，开发了一种包含装载脲酶B亚基（rUreB）的工程纳米颗粒的颊部微针贴片，以克服上述挑战。具体而言，开发了一种工程纳米载体来保护抗原并调节其释放曲线。然后，将纳米颗粒富集形成具有优异机械性能和防水性能的微针尖端，使其能够有效穿透颊黏膜并抵抗唾液冲刷。此外，微针呈现出S型抗原释放模式，这对于招募抗原呈递细胞（APC）以及下调黏膜耐受性树突状细胞（DC）和调节性T细胞（Treg）至关重要。不含任何免疫刺激剂的颊部微针疫苗可诱导强烈的全身和黏膜免疫反应，从而为小鼠提供卓越的保护，使其免受幽门螺杆菌的口服攻击。这些结果表明，合理设计的颊部微针疫苗能够有效克服黏膜递送障碍和黏膜耐受性，为亚单位抗原的黏膜疫苗接种提供了一种有前景的替代策略。
