Potential of Enzymatically Synthesized Hemozoin Analog as Th1 Cell Adjuvant

Author:

Hoshi Kazuaki1,Tu Anh Thi Tram123,Shobo Miwako1,Kettisen Karin4,Ye Lei4ORCID,Bülow Leif4ORCID,Hakamata Yoji5ORCID,Furuya Tetsuya6ORCID,Asano Ryutaro7ORCID,Tsugawa Wakako7ORCID,Ikebukuro Kazunori7ORCID,Sode Koji8ORCID,Yamazaki Tomohiko19ORCID

Affiliation:

1. Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), Tsukuba 305-0047, Japan

2. Department of Magnetic and Biomedical Materials, Faculty of Materials Science and Technology, University of Science, Ho Chi Minh City 70000, Vietnam

3. Ho Chi Minh City Campus, Vietnam National University, Ho Chi Minh City 70000, Vietnam

4. Division of Pure and Applied Biochemistry, Department of Chemistry, Lund University, 22100 Lund, Sweden

5. School of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University, Musashino 180-8602, Japan

6. Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu 183-8509, Japan

7. Department of Biotechnology and Life science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei 184-8588, Japan

8. Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA

9. Graduate School of Life Science, Hokkaido University, Sapporo 060-0808, Japan

Abstract

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.

Funder

Japan Society for the Promotion of Science Kakenhi

Japan Agency for Medical Research and Development (AMED) for the translational

clinical research core institutes under the Tsukuba Clinical Research & Development Organization

Publisher

MDPI AG

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