Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine

• Main Authors: Yunru Wang, Koji Hosomi, Atsushi Shimoyama, Ken Yoshii, Haruki Yamaura, Takahiro Nagatake, Tomomi Nishino, Hiroshi Kiyono, Koichi Fukase, Jun Kunisawa
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Vaccines
• Subjects: <i>Alcaligenes faecalis</i>; Th17; lipid A
• Online Access: https://www.mdpi.com/2076-393X/8/3/395

<i>Alcaligenes</i> spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that <i>Alcaligenes</i>-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 <i>Alcaligenes</i> lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus <i>Alcaligenes</i> lipid A relative to those that were immunized with OVA alone. In addition, <i>Alcaligenes</i> 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 <i>Alcaligenes</i> lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, <i>Alcaligenes</i> lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that <i>Alcaligenes</i> lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination.