Potential of Enzymatically Synthesized Hemozoin Analog as Th1 Cell Adjuvant
Kazuaki Hoshi,
Anh Thi Tram Tu,
Miwako Shobo,
Karin Kettisen,
Lei Ye,
Leif Bülow,
Yoji Hakamata,
Tetsuya Furuya,
Ryutaro Asano,
Wakako Tsugawa,
Kazunori Ikebukuro,
Koji Sode,
Tomohiko Yamazaki
Affiliations
Kazuaki Hoshi
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), Tsukuba 305-0047, Japan
Anh Thi Tram Tu
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), Tsukuba 305-0047, Japan
Miwako Shobo
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), Tsukuba 305-0047, Japan
Karin Kettisen
Division of Pure and Applied Biochemistry, Department of Chemistry, Lund University, 22100 Lund, Sweden
Lei Ye
Division of Pure and Applied Biochemistry, Department of Chemistry, Lund University, 22100 Lund, Sweden
Leif Bülow
Division of Pure and Applied Biochemistry, Department of Chemistry, Lund University, 22100 Lund, Sweden
Yoji Hakamata
School of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University, Musashino 180-8602, Japan
Tetsuya Furuya
Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu 183-8509, Japan
Ryutaro Asano
Department of Biotechnology and Life science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei 184-8588, Japan
Wakako Tsugawa
Department of Biotechnology and Life science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei 184-8588, Japan
Kazunori Ikebukuro
Department of Biotechnology and Life science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei 184-8588, Japan
Koji Sode
Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA
Tomohiko Yamazaki
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), Tsukuba 305-0047, Japan
Hemozoin (Hz) is a heme crystal produced during malaria infection that stimulates immune cells, leading to the production of cytokines and chemokines. The immunostimulatory action of Hz has previously been applied in the development of alternative adjuvants. Crystallization of hemin is a chemical approach for producing Hz. Here, we focused on an enzymatic production method for Hz using the heme detoxification protein (HDP), which catalyzes heme dimer formation from hemin in Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum HDP. Enzymatically synthesized Hz stimulates a macrophage cell line and human peripheral mononuclear cells, leading to the production of interleukin (IL)-6 and IL-12p40. In mice, subcutaneous administration of esHz together with an antigen, ovalbumin (OVA), increased the OVA-specific immunoglobulin (Ig) G2c isotype level in the serum, whereas OVA-specific IgG1 was not induced. Our findings suggest that esHz is a useful Th-1 cell adjuvant.
