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