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
Yunru Wang,
Koji Hosomi,
Atsushi Shimoyama,
Ken Yoshii,
Haruki Yamaura,
Takahiro Nagatake,
Tomomi Nishino,
Hiroshi Kiyono,
Koichi Fukase,
Jun Kunisawa
Affiliations
Yunru Wang
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
Koji Hosomi
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
Atsushi Shimoyama
Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan
Ken Yoshii
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
Haruki Yamaura
Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan
Takahiro Nagatake
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
Tomomi Nishino
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
Hiroshi Kiyono
International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Koichi Fukase
Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan
Jun Kunisawa
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
Alcaligenes spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that Alcaligenes-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 Alcaligenes lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus Alcaligenes lipid A relative to those that were immunized with OVA alone. In addition, Alcaligenes 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 Alcaligenes lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, Alcaligenes lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that Alcaligenes lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination.
