Engineered Norovirus-Derived Nanoparticles as a Plug-and-Play Cancer Vaccine Platform

In recent years, virus-derived self-assembled protein nanoparticles (NPs) have emerged as attractive antigen delivery platforms for developing both preventive and therapeutic vaccines. In this study, we exploited the genetically engineered Norovirus S domain (Nov-S) with SpyCatcher003 fused to the C-terminus to develop a robust, modular, and versatile NP-based carrier platform (Nov-S-Catcher003). The NPs can be conveniently armed in a plug-and-play pattern with SpyTag003-linked antigens. Nov-S-Catcher003 was efficiently expressed in Escherichia coli and self-assembled into highly uniform NPs with a purified protein yield of 97.8 mg/L. The NPs presented high stability at different maintained temperatures and after undergoing differing numbers of freeze-thaw cycles. Tumor vaccine candidates were easily obtained by modifying Nov-S-Catcher003 NPs with SpyTag003-linked tumor antigens. Nov-S-Catcher003-antigen NPs significantly promoted the maturation of bone marrow-derived dendritic cells in vitro and were capable of efficiently migrating to lymph nodes in vivo. In TC-1 and B16F10 tumor-bearing mice, the subcutaneous immunization of NPs elicited robust tumor-specific T-cell immunity, reshaped the tumor microenvironment, and inhibited tumor growth. In the TC-1 model, the NPs even completely abolished established tumors. In conclusion, the Nov-S-Catcher003 system is a promising delivery platform for facilitating the development of NP-based cancer vaccines.

Automated summary

In recent years, virus-derived self-assembled protein nanoparticles (NPs) have been used as antigen delivery platforms for vaccines. In this study, a genetically engineered Norovirus S domain (Nov-S) with SpyCatcher003 was developed as a versatile NP-based carrier platform. The NPs showed high stability and could be easily modified with tumor antigens. In vitro and in vivo experiments demonstrated that the NPs promoted dendritic cell maturation and induced robust tumor-specific T-cell immunity, inhibiting tumor growth. This study suggests that the Nov-S-Catcher003 system is a promising platform for NP-based cancer vaccines.