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Description:

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.

Rights:

• Creative Commons BY Attribution 4.0 International
  

Keyword: hemozoin analog, heme detoxification protein, adjuvant, vaccine, Th-1 immunity

Date published: 2024-09-03

Publisher: MDPI AG

Journal:

• Nanomaterials (ISSN: 20794991) vol. 14 issue. 17 1440

Funding:

• Japan Society for the Promotion of Science Kakenhi 17KK0122 (植物・微生物由来ヘミンからの免疫活性化ヘムポリマーの合成)
• Japan Society for the Promotion of Science Kakenhi 15K06589 (ヘミン誘導体から構成される免疫活性化剤の開発)
• AMED, Clinical research core institutes under the Tsukuba Clinical Research & Development Organization A18-58 (AMED 橋渡し研究戦略的推進プログラム アジュバントとして機能する酵素合成ヘモゾインナノ粒⼦の開発)

Manuscript type: Publisher's version (Version of record)

MDR DOI:

First published URL: https://doi.org/10.3390/nano14171440

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Updated at: 2024-10-04 12:30:16 +0900

Published on MDR: 2024-10-04 12:30:18 +0900