Wang Yunru, Hosomi Koji, Shimoyama Atsushi, Yoshii Ken, Yamaura Haruki, Nagatake Takahiro, Nishino Tomomi, 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 Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Vaccines (Basel). 2020 Jul 20;8(3):395. doi: 10.3390/vaccines8030395.
spp. are identified as commensal bacteria and have been found to inhabit Peyer's patches in the gut. We previously reported that -derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible for the biological effect of LPS and has previously been applied as an adjuvant. Here, we examined the adjuvant activity and safety of chemically synthesized lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus lipid A relative to those that were immunized with OVA alone. In addition, lipid A promoted antigen-specific T helper 17 (Th17) responses in the spleen; upregulated the expression of MHC class II, CD40, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs); enhanced the production of Th17-inducing cytokines IL-6 and IL-23 from BMDCs. Stimulation with lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination.
某属细菌被鉴定为共生菌，并已发现其栖息于肠道的派尔集合淋巴结中。我们之前报道过，源自某属的脂多糖（LPS）在全身疫苗接种中发挥佐剂活性，且不会引发过度炎症。脂质A是负责LPS生物学效应的成分之一，此前已被用作佐剂。在此，我们检测了化学合成脂质A的佐剂活性和安全性。我们发现，相对于仅用卵清蛋白（OVA）免疫的小鼠，用OVA加脂质A皮下免疫的小鼠中OVA特异性血清IgG抗体水平升高。此外，脂质A促进了脾脏中抗原特异性辅助性T细胞17（Th17）反应；上调了骨髓来源树突状细胞（BMDC）上MHC II类、CD40、CD80和CD86的表达；增强了BMDC产生Th17诱导细胞因子IL-6和IL-23的能力。用脂质A刺激还诱导了人外周血单核细胞中IL-6和IL-1β的产生。此外，脂质A引起了诸如淋巴细胞减少和血小板减少等轻微副作用。这些发现表明，脂质A通过在全身疫苗接种中直接刺激树突状细胞，是一种安全有效的Th17型佐剂。
