Adjuvant activity of Mycobacteria-derived mycolic acids
Mio Kubota,
Ei'ichi Iizasa,
Yasushi Chuuma,
Hideyasu Kiyohara,
Hiromitsu Hara,
Hiroki Yoshida
Affiliations
Mio Kubota
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, 849-8501, Japan; Saga-ken Medical Center Koseikan, Saga, 840-8571, Japan
Ei'ichi Iizasa
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, 849-8501, Japan; Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, 890-8544, Japan
Yasushi Chuuma
Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, 204-0022, Japan
Hideyasu Kiyohara
Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, 204-0022, Japan
Hiromitsu Hara
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, 849-8501, Japan; Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, 890-8544, Japan
Hiroki Yoshida
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, 849-8501, Japan; Corresponding author.
Successful vaccination, especially with safe vaccines such as component/subunit vaccines, requires proper activation of innate immunity and, for this purpose, adjuvant is used. For clinical use, alum is frequently used while, for experimental use, CFA, containing Mycobacterial components, was often used. In this report, we demonstrated that mycolic acids (MA), major and essential lipid components of the bacterial cell wall of the genus Mycobacterium, has adjuvant activity. MA plus model antigen-immunization induced sufficient humoral response, which was largely comparable to conventional CFA plus antigen-immunization. Importantly, while CFA plus antigen-immunization induced Th17-biased severe and destructive inflammatory responses at the injected site, MA plus antigen-immunization induced Th1-biased mild inflammation at the site. MA induced dendritic cell activation by co-stimulatory molecule induction as well as inflammatory cytokine/chemokine induction. MA plus antigen-immunization successfully protected mice from tumor progression both in prevention and in therapy models. We thus submit that MA is a promising adjuvant candidate material for clinical purposes and for experimental purposes from a perspective of animal welfare.
