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A candidate tick-borne encephalitis virus vaccine based on virus-like particles induces specific cellular and humoral immunity in mice

Mengyao Zhang, Hongli Jin, -Cuicui Jiao, Yuanyuan Zhang, Yujie Bai, Zhiyuan Gong, Pei Huang, Haili Zhang, Yuanyuan Li#, Hualei Wang#

State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Jilin 130062, China

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摘要  

蜱传脑炎(Tick-borne encephalitisTBE)是由蜱传播的一种重要的人畜共患病毒病。近几十年来,由于全球气候变暖,导致人类接触蜱虫的机会增该病的死亡率也逐渐上升。由于缺乏特异性抗病毒治疗,有效的疫苗免疫对于控制 TBE 至关重要。基于病毒样颗粒(Virus-like particlesVLPs)的候选疫苗已被证明能有效激发机体产生针对流感病毒和新冠病毒的免疫反应。本文利用昆虫细胞-杆状病毒表达系统构建了含有来自远东 TBEV 株(WH2012)的包膜蛋白和膜蛋白的 TBEV VLPs(图1,并研究小鼠肌肉注射TBEV VLPs 候选疫苗(使用 Poly(I:C) Montanide ISA 201VG 作为联合佐剂)后的免疫应答产生情况:TBEV VLPs 在免疫后可被小鼠的树突状细胞(Dendritic cellsDCs)捕获成熟的 DCs 将TBEV VLPs表面抗原提呈给T细胞,激活T细胞的免疫应答反应;在T细胞的辅助下,B细胞进一步成熟和活化,产生特异性的细胞和体液免疫应答;血清特异性IgG抗体水平可达 1:104.6,并且在三次免疫后的24周内一直保持在 1:104经过三次免疫后,TBEV VLPs 在小鼠体内产生了特异性记忆T细胞。综上所述TBEV VLPs 具有良好的免疫原性,不仅能刺激小鼠产生特异性免疫反应,具有很高的安全性,可作为 TBEV 候选疫苗,为开发抗 TBEV 的新型基因工程疫苗奠定了基础。



Abstract  

Tick-borne encephalitis (TBE) is an important zoonotic viral disease transmitted by ticks. In recent decades, global climate change has increased human exposure to ticks, and mortality rates have gradually risen. Effective vaccines are essential for controlling TBE as specific antiviral treatment is unavailable. Vaccine candidates based on virus-like particles (VLPs) have previously been demonstrated to be efficient in eliciting excellent immune responses against influenza virus and SARS-CoV-2. Here, we constructed TBE virus (TBEV) VLPs containing the envelope and membrane proteins derived from the Far Eastern TBEV strain (WH2012) using an insect cell-baculovirus expression system. Induction of immune responses was investigated in mice following intramuscular injection with the TBEV VLPs vaccine candidates formulated of Poly(I:C) & Montanide ISA 201VG combination adjuvants. Mice produced memory T-cells and serum-specific IgG antibodies that averaged up to 1:104.6 and remained at 1:104 (mean) for 24 weeks after three immunizations. TBEV VLPs vaccine was able to provide long-term antibody protection against TBEV, making it a promising subunit vaccine candidate for this disease.

Keywords:  tick-borne encephalitis virus       virus-like particles        envelope protein        subunit vaccine  
Online: 26 September 2024  
Fund: This work was supported by the National Key Research and Development Program of China (2021YFC2600202) and the Fundamental Research Funds for the Central Universities (2132020KJC016).
About author:  Mengyao Zhang, E-mail: zhangmy1233@163.com; #Correspondence Hualei Wang, E-mail: wanghualei@jlu.edu.cn; Yuanyuan Li, E-mail: li_yuanyuan@jlu.edu.cn. * These authors contributed equally to this study.

Cite this article: 

Mengyao Zhang, Hongli Jin, Cuicui Jiao, Yuanyuan Zhang, Yujie Bai, Zhiyuan Gong, Pei Huang, Haili Zhang, Yuanyuan Li, Hualei Wang. 2024. A candidate tick-borne encephalitis virus vaccine based on virus-like particles induces specific cellular and humoral immunity in mice. Journal of Integrative Agriculture, Doi:10.1016/j.jia.2024.09.024

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