PDF(Pubmed)
Abstract：
The acidic environment and enzyme degradation lead to oral vaccines often having little immune effect. Therefore, it is an attractive strategy to study an effective and safe oral vaccine delivery system that can promote gastrointestinal mucosal immune responses and inhibit antigen degradation. Moreover, the antigens uptake by microfold cells (M cells) is the determining step in initiating efficient immune responses. Therefore, M cell-targeting is one promising approach for enhancing oral vaccine potency. In the present study, an M cell-targeting L. lactis surface display system (plSAM) was built to favor the multivalent epitope vaccine antigen (FAdE) to achieve effective gastrointestinal mucosal immunity against Helicobacter pylori. Therefore, a recombinant Lactococcus lactic acid vaccine (LL-plSAM-FAdE) was successfully prepared, and its immunological properties and protective efficacy were analyzed. The results showed that LL-plSAM-FAdE can secretively express the recombinant proteins SAM-FAdE and display the SAM-FAdE on the bacterial cell surface. More importantly, LL-plSAM-FAdE effectively promoted the phagocytosis and transport of vaccine antigen by M cells in the gastrointestinal tract of mice, and simulated high levels of cellular and humoral immune responses against four key H. pylori adhesins (Urease, CagL, HpaA, and Lpp20) in the gastrointestinal tract, thus enabling effective prevention of H. pylori infection and to some extent eliminating H. pylori already present in the gastrointestinal tract. KEY POINTS: • M-cell-targeting L. lactis surface display system LL- plSAM was designed • This system displays H. pylori vaccine-promoted phagocytosis and transport of M cell • A promising vaccine candidate for controlling H. pylori infection was verified.
摘要：
酸性环境和酶降解导致口服疫苗通常几乎没有免疫效果。因此,研究一种能促进胃肠道黏膜免疫反应和抑制抗原降解的有效和安全的口服疫苗给药系统是一个有吸引力的策略。此外，微折叠细胞(M细胞)对抗原的摄取是启动有效免疫应答的决定步骤。因此,M细胞靶向是增强口服疫苗效力的一种有前途的方法。在本研究中,建立了一种M细胞靶向的乳酸乳球菌表面展示系统（plSAM），以支持多价表位疫苗抗原（FAdE）实现针对幽门螺杆菌的有效胃肠道粘膜免疫。因此,成功制备了重组乳酸乳球菌疫苗(LL-plSAM-FAdE),并对其免疫学特性和保护效果进行了分析。结果表明，LL-plSAM-FAdE可以分泌表达重组蛋白SAM-FAdE，并在细菌细胞表面展示SAM-FAdE。更重要的是,LL-plSAM-FAdE有效促进M细胞在小鼠胃肠道内吞噬和转运疫苗抗原,和模拟高水平的细胞和体液免疫反应，针对四种关键的幽门螺杆菌粘附素（脲酶，卡格,Hpaa,和Lpp20）在胃肠道中，从而能够有效预防幽门螺杆菌感染，并在一定程度上消除已经存在于胃肠道中的幽门螺杆菌。关键点:•设计了M-细胞靶向乳酸乳球菌表面展示系统LL-plSAM•该系统展示了幽门螺杆菌疫苗促进的M细胞的吞噬作用和转运•验证了用于控制幽门螺杆菌感染的有希望的候选疫苗。
