摘要
水痘带状疱疹病毒(Varicella-zoster virus,VZV)是引起全球老年人带状疱疹(Herpes zoster,HZ)的主要病原体,VZV gE蛋白是诱导机体产生免疫应答的主要结构蛋白,基于gE蛋白设计的重组蛋白疫苗Shingrix已经在我国批准上市。多种研究表明聚体蛋白可以诱导更强的免疫应答,本研究应用中国仓鼠卵巢细胞CHO-S表达连接Foldon结构域的蛋白(gE-Foldon)、连接Fc片段的蛋白(gE-Fc)和gE蛋白。三种抗原(gE-Foldon、gE-Fc和gE)分别联合AlOH+CpG佐剂,比较在BALB/c小鼠中的免疫效果,同时,将商品化的Shingrix作为对照。SDS-PAGE和WB结果显示成功表达纯化三种抗原,非还原条件下可以观察到gE-Foldon以三聚体形式存在。与gE和gE-Fc抗原相比,gE-Foldon在小鼠中诱导产生的IgG抗体(40492)和中和抗体滴度(1190.5)最高(P<0.01),与Shingrix相当。此外gE-Foldon诱导小鼠产生的分泌IL-2、IL-4的淋巴细胞数量显著高于其他免疫组(P<0.0001,P<0.05)。综上所述,gE-Foldon蛋白联合AlOH+CpG佐剂可诱导较强的体液和细胞免疫应答,因此可以作为预防HZ的潜在候选疫苗。
Varicella-zoster virus(VZV)is the main pathogen that causes Herpes zoster(HZ)infection in the elderly worldwide.VZV gE protein is the main structural protein that induces immune responses in the body.Shingrix,a recombinant protein vaccine designed based on gE protein,has been approved for use in China.Several studies have shown that polymeric proteins can induce stronger immune responses.Herein,Chinese hamster ovarian cells CHO-S were used to express the Foldon domain-linked protein(ge-Foldon),Fc domainlinked protein(ge-Fc)and gE proteins.The immune effects of the three antigens(ge-Foldon,ge-Fc and gE)combined with AIOH+CpG adjuvant were compared in BALB/c mice.Meanwhile,commercial Shingrix was used as a control.Results from sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting showed that the three antigens were successfully expressed and purified,and gE-Foldon was observed to be a trimer under non-reducing conditions.Compared with gE and ge-Fc antigens,ge-Foldon induced the highest titers of IgG antibodies(40492)and neutralizing antibodies(1190.5)in mice(P<0.01),which were comparable to those induced by Shingrix.The number of interleukin IL-2 and IL-4 secreting lymphocytes induced by gE-Foldon was significantly higher than that of other immunization groups(P<0.0001,P<0.05).In conclusion,gE-Foldon protein in combination with AIOH+CpG adjuvant induced strong humoral and cellular immune responses and thus could be used as a potential vaccine candidate for the prevention of HZ infection.
作者
李海鑫
曹蕾
郭晋源
孙馨
胡宏俏
时雨晴
张丽
武婕慧
谢智博
张瑶
张燕
李海
李栋
LI Haixin;CAO Lei;GUO Jinyuan;SUN Xin;HU Hongqiao;SHI Yuqing;ZHANG Li;WU Jiehui;XIE Zhibo;ZHANG Yao;ZHANG Yan;LI Hai;LI Dong(Shandong First Medical University&Shandong Academy of Medical Sciences,School of Public Health and Health Management,Jinan 250117,China;NHC Key Laboratory of Medical Virology and Viral Diseases,National Institute for Viral Disease Control and Prevention,Chinese Center forDisease Control and Prevention,Beijing 102206,China)
出处
《病毒学报》
CAS
CSCD
北大核心
2024年第2期314-325,共12页
Chinese Journal of Virology
作者简介
李海鑫(1997-),男,从事水痘带状疱疹病毒亚单位疫苗的研究,Email:976377780@qq.com;通讯作者:李海(1990-),男,副研究员,从事人呼吸道合胞病毒以及水痘带状疱疹病毒等多种病毒疫苗的研究,Email:lihai@ivdc.chinacdc.cn;通讯作者:李栋(1969-),男,教授,从事慢性病与糖基组学研究,Email:tsmcdongli@163.com。
