Yoshii Ken, Hosomi Koji, Shimoyama Atsushi, Wang Yunru, Yamaura Haruki, Nagatake Takahiro, Suzuki Hidehiko, Lan Huangwenxian, Kiyono Hiroshi, Fukase Koichi, Kunisawa Jun
Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan.
Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Microorganisms. 2020 Jul 23;8(8):1102. doi: 10.3390/microorganisms8081102.
Effective and safe vaccine adjuvants are needed to appropriately augment mucosal vaccine effects. Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer's patch resident stimulated dendritic cells to promote the production of mucosal immunity-enhancing cytokines (e.g., IL-6 and BAFF), thus enhancing antigen-specific immune responses (including IgA production and Th17 responses) without excessive inflammation. Here, we chemically synthesized lipid A, the biologically active part of LPS, and examined its efficacy as a nasal vaccine adjuvant for the induction of protectively immunity against infection. Mice were nasally immunized with pneumococcal surface protein A (PspA) as a vaccine antigen for , together with lipid A. lipid A supported the generation of high levels of PspA-specific IgA and IgG responses through the augmentation of germinal center formation in the nasopharynx-associated lymphoid tissue and cervical lymph nodes (CLNs). Moreover, lipid A promoted PspA-specific CD4 Th17 responses in the CLNs and spleen. Furthermore, neutrophils were recruited to infection sites upon nasal infection and synchronized with the antigen-specific T and B cell responses, resulting in the protection against infection. Taken together, lipid A could be applied to the prospective adjuvant to enhance nasal vaccine efficacy by means of augmenting both the innate and acquired arms of mucosal immunity against respiratory bacterial infection.
需要有效且安全的疫苗佐剂来适当增强黏膜疫苗的效果。我们之前的研究表明，派尔集合淋巴结驻留菌的脂多糖（LPS）可刺激树突状细胞，促进黏膜免疫增强细胞因子（如IL-6和BAFF）的产生，从而增强抗原特异性免疫反应（包括IgA产生和Th17反应），且不会引发过度炎症。在此，我们化学合成了LPS的生物活性部分脂质A，并检测了其作为鼻用疫苗佐剂诱导针对感染的保护性免疫的功效。将肺炎球菌表面蛋白A（PspA）作为疫苗抗原与脂质A一起经鼻免疫小鼠。脂质A通过增强鼻咽相关淋巴组织和颈淋巴结（CLNs）中生发中心的形成，支持高水平PspA特异性IgA和IgG反应的产生。此外，脂质A促进了CLNs和脾脏中PspA特异性CD4 Th17反应。此外，在鼻内感染时，中性粒细胞被募集到感染部位，并与抗原特异性T和B细胞反应同步，从而实现对感染的保护。综上所述，脂质A可作为一种前瞻性佐剂，通过增强黏膜免疫的固有和获得性分支来提高鼻用疫苗对呼吸道细菌感染的功效。
