Development of a novel virus-like particle-based vaccine for preventing tick-borne encephalitis virus infection

Jielin Tang; Muqing Fu; Chonghui Xu; Bao Xue; Anqi Zhou; Sijie Chen; He Zhao; Yuan Zhou; Jizheng Chen; Qi Yang; Xinwen Chen

doi:10.1016/j.virs.2023.06.003

Development of a novel virus-like particle-based vaccine for preventing tick-borne encephalitis virus infection

Virol Sin. 2023 Oct;38(5):767-777. doi: 10.1016/j.virs.2023.06.003. Epub 2023 Jun 14.

Authors

Jielin Tang¹, Muqing Fu², Chonghui Xu³, Bao Xue¹, Anqi Zhou⁴, Sijie Chen⁴, He Zhao³, Yuan Zhou³, Jizheng Chen⁵, Qi Yang⁶, Xinwen Chen⁷

Affiliations

¹ Guangzhou National Laboratory, Guangzhou, 510005, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
² Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
³ State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
⁴ GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
⁵ Guangzhou National Laboratory, Guangzhou, 510005, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, 511436, China.
⁶ Guangzhou National Laboratory, Guangzhou, 510005, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China. Electronic address: yang_qi@gzlab.ac.cn.
⁷ Guangzhou National Laboratory, Guangzhou, 510005, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, 511436, China. Electronic address: chen_xinwen@gzlab.ac.cn.

Abstract

Tick-borne encephalitis virus (TBEV) is an important tick-borne pathogen that poses as a serious public health concern. The coverage and immunogenicity of the currently available vaccines against TBEV are relatively low; therefore, it is crucial to develop novel and effective vaccines against TBEV. The present study describes a novel strategy for the assembly of virus-like particles (VLPs) by co-expressing the structural (core/prM/E) and non-structural (NS2B/NS3Pro) proteins of TBEV. The efficacy of the VLPs was subsequently evaluated in C57BL/6 mice, and the resultant IgG serum could neutralize both Far-Eastern and European subtypes of TBEV. These findings indicated that the VLP-based vaccine elicited the production of cross-subtype reactive antibodies. The VLPs provided protection to mice lacking the type I interferon receptor (IFNAR^-/-) against lethal TBEV challenge, with undetectable viral load in brain and intestinal tissues. Furthermore, the group that received the VLP vaccine did not exhibit significant pathological changes and the inflammatory factors were significantly suppressed compared to the control group. Immunization with the VLP vaccine induced the production of multiple-cytokine-producing antiviral CD4⁺ T cells in vivo, including TNF-α⁺, IL-2⁺, and IFN-γ⁺ T cells. Altogether, the findings suggest that noninfectious VLPs can serve as a potentially safe and effective vaccine candidate against diverse subtypes of TBEV.

Keywords: Immunogenicity; Neutralization; Tick-borne encephalitis virus (TBEV); Vaccine; Virus-like particle (VLP).

MeSH terms

Animals
Antibodies, Viral
Encephalitis Viruses, Tick-Borne* / genetics
Encephalitis, Tick-Borne* / prevention & control
Mice
Mice, Inbred C57BL
Vaccines, Virus-Like Particle* / genetics

Substances

Vaccines, Virus-Like Particle
Antibodies, Viral