首页|水痘带状疱疹病毒gE-Foldon融合蛋白的表达及免疫效果的分析

水痘带状疱疹病毒gE-Foldon融合蛋白的表达及免疫效果的分析

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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,VZVgE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.
Expression and Immune Effect of gE-Foldon Fusion Protein of Varicella Zoster Virus
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 domain-linked protein(ge-Fc)and gE proteins.The immune effects of the three antigens(ge-Foldon,ge-Fc and gE)combined with AlOH+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 AlOH+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.

Varicella-zoster virusgE-Foldon proteinImmune effect

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

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山东第一医科大学山东省医学科学院公共卫生与健康管理学院,济南 250117

国家卫生健康委医学病毒和病毒病重点实验室中国疾病预防控制中心病毒病预防控制所,北京 102206

水痘带状疱疹病毒 gE-Foldon蛋白 免疫效果

2024

病毒学报
中国微生物学会

病毒学报

CSTPCD北大核心
影响因子:1.046
ISSN:1000-8721
年,卷(期):2024.40(2)
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