Kyushu University succeeds at direct activation of human immune cells via adjuvant production from crab shells

Crab shells may soon become usable to develop adjuvants (immunostimulants) for vaccines and other products. A research group led by Graduate Student Risa Hatase at Kyushu University's Graduate School of Bioresource and Bioenvironmental Sciences, and Specially Appointed Assistant Professor Qi Li, Assistant Professor Mayumi Hatakeyama, and Professor Takuya Kitaoka of the Faculty of Agriculture at Kyushu University cultured Toll-like receptor (TLR)2-expressing HEK293 cells and human monocytes using nanofibers of crab-derived chitin, a natural polysaccharide, as culture substrates. The research group found that solid polysaccharide nanofibers were capable of directly activating TLR2 receptors. They performed specific deacetylation of the chitin nanofiber surface and thereby prepared polysaccharide-based substrate materials with different surface glycan structures. In addition, they revealed that the human immune responses were regulated via a mechanism dependent on the surface N-acetylglucosamine content of the substrates. The study was published in the International Journal of Biological Macromolecules.

Adjuvants, which activate innate immunity, enhance the efficacy of vaccines and other drugs. They are expected to mitigate the effects of individual differences in humans, reduce the required antigen contents in vaccines and the required number of vaccine shots, and improve the effectiveness of medication in newborns and elderly people with weak immunity. However, adjuvants approved in Japan are scarce, and these are limited to aluminum salts and oil emulsions.

Recently, TLR agonist adjuvants based on the mechanism of TLRs, which detect various pathogens and control innate immunity, have attracted attention, and there are growing expectations for the development of safe and reliable TLR agonists.

The research group discovered that structurally well-defined chitin nanofibers (CtNFs) isolated from crab shells were capable of directly activating TLRs on the surface of human immune cells. Using CtNFs from crustaceans as a cell culture scaffold, they cultured cells of the human embryonic kidney HEK293 cell line expressing TLR2, one of the 10 TLRs expressed in humans, and human monocytic THP1 cells and found that immune responses were activated in a manner dependent on the surface CtNF amount of the substrates. They also found that specific deacetylation of the CtNF surface abolished the immune response and that the immune response could be regulated in a manner dependent on the surface N-acetylglucosamine amount of the substrate.

Accordingly, TLR2 on human immune cells was shown to directly recognize nano-sized solid-state CtNF as an agonist. Modification and control of the surface structure of CtNF, a natural polysaccharide derived from fishery waste, are expected to lead to establishing the efficacy of TLR agonists, which are promising as vaccine adjuvants, to develop novel drug modalities.

Journal Information
Publication: International Journal of Biological Macromolecules
Title: Direct activation of Toll-like receptor 2 signaling stimulated by contact with the interfacial structures of chitin nanofibers
DOI: 10.1016/j.ijbiomac.2024.138092