Dimerization: A structural feature for the protection of Hepatitis E virus capsid protein against trypsinization

Zhou

et al. 2021

Intervirology

Introduction: Virus-like particles (VLPs), self-assembled multiprotein structures, can stimulate robust immune responses due to their structural similarity to native virions that allow the presentation of 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 investigates the potential of the truncated hepatitis E virus (HEV) capsid as a VLP platform to present foreign antigens. Methods: The S and M domains of the HEV capsid protein were selected as the optimal carrier (CaSM). The exogenous antigen Seq8 containing 3 neutralizing epitopes from 3 different foot-and-mouth disease virus (FMDV) strains was linked to the C-terminal of CaSM to construct a chimeric VLP (CaSM-Seq8). The chimeric particles were produced in Escherichia coli, and their morphology, physicochemical properties, antigenicity, and immunogenicity were analyzed. Results: Morphological analysis showed that CaSM-Seq8 self-assembled into VLPs similar to CaSM VLPs (∼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 the CaSM carrier. The antigenicity analysis revealed a more robust reactivity against anti-FMDV antibodies when Seq8 was presented on 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. Conclusion: This study demonstrated the potential of utilizing the truncated HEV capsid as an antigen-presenting platform for the development of chimeric VLP immunogens.

Section: Computational Analysis Of the Oligomerization States Of The Target Proteinsmentioning

confidence: 99%

Hepatitis E Virus Capsid as a Carrier of Exogenous Antigens for the Development of Chimeric Virus-Like Particles

Zhou

et al. 2021

Intervirology

“…The Phyre2 server 29 was used to predict the 3D structures of CaSM, CaSM-Seq8, and Seq8; and the models were refined using GalaxyWeb Refine server 30 as previously described 31 . Then, GalaxyWeb Homomer server 32 was used to predict the oligomerization state and assembly pattern based on the monomer's 3D structures.…”

Section: Computational Analysis Of the Oligomerization States Of The mentioning

confidence: 99%

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

Lu¹,

Baha³

et al. 2020

Preprint

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.

“…The 3D structures of the target proteins were predicted using phyre2 server [34], and refined by GalaxyWeb Refine server [35] as previously described [36]. Then, GalaxyWeb Homomer server [26] was used to predict the oligomerization state from the monomer 3D structures.…”

Section: Computational Analysis Of the Oligomerization State Of The Tmentioning

confidence: 99%

Hepatitis E virus truncated capsid protein as a potential carrier of exogenous antigens for the development of chimeric virus-like particle vaccines

Lu¹,

Zhou³

et al. 2019

Preprint

Background: Virus like particle (VLP), a multiprotein structure which is assembled automatically, can stimulate robust immune responses due to an appropriate size, repetitive epitopes, and a structure similar to native virions. Utilizing VLPs as vaccine carriers to present exogenous antigens is a promising and challenging field in vaccine design. Hence, this study aims to investigate the potential of Hepatitis E virus (HEV) truncated capsid protein as a VLP carrier presenting foreign antigens in vaccine design.Results: S and M domains of HEV ORF2 protein (aa112-455) were selected as an optimal carrier (CaSM). The exogenous antigen Seq8 containing three immunogenic domains from three different foot-and-mouth disease virus (FMDV) strains was linked to the C-terminal of CaSM to construct a chimeric VLP vaccine candidate (CaSM-Seq8). Morphological analysis showed that CaSM-Seq8 self-assembled into VLPs with a diameter of approximately 26 nm, similar to the VLPs of CaSM alone but smaller than native HEV virions. Further, the thermal stability and the proteolysis resistance of Seq8 were enhanced when carried by CaSM. The antigenicity analysis revealed a more robust reactivity against anti-FMDV specific antibodies when Seq8 was presented on the CaSM particles. Upon injection into mice, anti-FMDV IgGs induced by CaSM-Seq8 appeared earlier, increased faster, and maintained higher levels for a longer time than those induced by Seq8 antigen alone or a commercial inactivated FMDV vaccine.Conclusions: This study demonstrates the potential of the HEV truncated capsid protein VLPs as a presenting-platform of exogenous antigens in vaccine design and promising preliminary results on chimeric VLP vaccine against foot-and-mouth disease.