Vilander Allison C, Shelton Kimberly, LaVoy Alora, Dean Gregg A
Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Vaccines (Basel). 2023 Jun 27;11(7):1162. doi: 10.3390/vaccines11071162.
The development of lactic acid bacteria as mucosal vaccine vectors requires the identification of robust mucosal adjuvants to increase vaccine effectiveness. The type I fimbriae adhesion protein FimH is of interest as a mucosal adjuvant as it targets microfold (M) cells enhancing vaccine uptake into Peyer's patches and can activate the innate immune system via Toll-like receptor (TLR) 4 binding. Here, we displayed the N-terminal domain of FimH on the surface of a vaccine vector and evaluated its ability to increase uptake of into Peyer's patches and activate innate immune responses. FimH was robustly displayed on the surface but did not increase uptake into the Peyer's patches. FimH did increase trafficking of to mesenteric lymph nodes by antigen-presenting cells including macrophages and dendritic cells. It also increased transcription of retinaldehyde dehydrogenase and decreased transcription of IL-21 in the Peyer's patches and mesenteric lymph nodes. The N-terminal domain of FimH did not activate TLR4 in vitro, indicating that FimH may stimulate innate immune responses through a not-yet-identified mechanism. These results indicate that FimH alters the innate immune response to and should be further studied as an adjuvant for lactic acid bacterial vaccine platforms.
将乳酸菌开发为黏膜疫苗载体需要鉴定强效的黏膜佐剂以提高疫苗效力。I型菌毛黏附蛋白FimH作为一种黏膜佐剂备受关注，因为它靶向微褶（M）细胞，增强疫苗向派尔集合淋巴结的摄取，并且可以通过Toll样受体（TLR）4结合激活先天免疫系统。在此，我们将FimH的N端结构域展示在疫苗载体表面，并评估其增加[具体物质]向派尔集合淋巴结摄取以及激活先天免疫反应的能力。FimH在[疫苗载体]表面大量展示，但并未增加向派尔集合淋巴结的摄取。FimH确实增加了包括巨噬细胞和树突状细胞在内的抗原呈递细胞将[具体物质]转运至肠系膜淋巴结的能力。它还增加了派尔集合淋巴结和肠系膜淋巴结中视黄醛脱氢酶的转录，并降低了IL-21的转录。FimH的N端结构域在体外未激活TLR4，这表明FimH可能通过一种尚未明确的机制刺激先天免疫反应。这些结果表明，FimH改变了对[具体物质]的先天免疫反应，应作为乳酸菌疫苗平台的佐剂进行进一步研究。
