Hepatitis E virus capsid as a carrier of exogenous antigens for the development of chimeric virus-like particles

Virus-like particle (VLP), a self-assembled multiprotein structure, can stimulate robust immune responses due to its structure similar to native virions that curries multiple copies of the target epitopes. Utilizing VLPs as vaccine platforms to present exogenous antigens is a promising and challenging approach in the vaccine development field. This study aims to investigate the potential of hepatitis E virus (HEV) truncated capsid as a VLP platform to present foreign antigens. The S and M domains of HEV capsid protein were selected as the optimal carrier (CaSM). The exogenous antigen Seq8 containing three neutralizing epitopes from three different foot-and-mouth disease virus (FMDV) strains was linked to the C-terminal of CaSM to construct a chimeric VLP (CaSM-Seq8). The construct was successfully expressed and purified. Morphological analysis showed that CaSM-Seq8 self-assembled into VLPs similar to CaSM VLP (~26 nm in diameter) but smaller than native HEV virions. Further, the thermal stability and the resistance to enzymatic proteolysis of Seq8 were enhanced when it was attached to CaSM carrier. The antigenicity analysis revealed a more robust reactivity against anti-FMDV antibodies when Seq8 was presented on the CaSM particles. Upon injection into mice, FMDV-specific IgGs induced by CaSM-Seq8 appeared earlier, increased faster, and maintained higher levels for a longer time than those induced by Seq8 alone or the inactivated FMDV vaccine. This study demonstrated the potential of utilizing HEV truncated capsid as an antigen-presenting platform for the development of chimeric VLP vaccines.