Alum/CpG修饰的西尼罗河病毒截短包膜蛋白诱导小鼠产生强大的体液免疫和T细胞免疫

IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Biosafety and Health Pub Date : 2023-10-01 DOI:10.1016/j.bsheal.2023.06.003
Yongping Du , Yao Deng , Ying Zhan , Ren Yang , Jiao Ren , Wen Wang , Baoying Huang , Wenjie Tan
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引用次数: 0

摘要

西尼罗河病毒(WNV)是一种蚊子传播的黄病毒,在全球分布数十年,可导致人类和动物疾病。到目前为止,还没有一种WNV疫苗获得人类使用许可。因此,开发新的候选疫苗和改进疫苗接种策略势在必行。由于WNV包膜(E)糖蛋白在介导病毒与细胞受体的结合和病毒细胞膜融合中发挥着重要作用,它是宿主体液反应的关键靶点。在这里,我们制备了WNV的重组截短包膜蛋白(rWNV-80E),并开发了一种以氢氧化铝(明矾)和合成寡核苷酸CpG为佐剂的WNV亚单位疫苗制剂。C57BL/6小鼠用5µg用Alum/CpG佐剂纯化的rWNV-80E肌肉内免疫两次,间隔28天。用酶联免疫吸附法检测WNV E特异性IgG,用单轮感染颗粒检测中和抗体(nAbs)。此外,通过酶联免疫斑点法和细胞内细胞因子染色法检测T细胞免疫。值得注意的是,rWNV-80E具有高度免疫原性,并引发强大的体液和细胞免疫,如小鼠T细胞中IFN-γ和TNF-α分泌的显著水平所证明的那样。总之,Alum/CpG佐剂rWNV-80E亚单位疫苗在小鼠中引发了强大且平衡的B细胞和T细胞免疫,因此它是一种有前景的候选疫苗,值得进一步研究用于人类或兽医应用。
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The recombinant truncated envelope protein of West Nile virus adjuvanted with Alum/CpG induces potent humoral and T cell immunity in mice

West Nile virus (WNV) is a mosquito-transmitted flavivirus distributed globally for decades and can cause disease in humans and animals. So far, no WNV vaccine has been licensed for human use. Therefore, the development of novel candidate vaccines and the improvement of vaccination strategies is imperative. As the WNV envelope (E) glycoprotein plays an important role in mediating viral binding to cellular receptors and virus-cell membrane fusion, it is a critical target for the host humoral response. Here, we prepared a recombinant truncated envelope protein of WNV (rWNV-80E) and developed a WNV subunit vaccine formulation with a combination of aluminum hydroxide (alum) and a synthetic oligonucleotide CpG as adjuvants. C57BL/6 mice were immunized twice intramuscularly at 28-day intervals with 5 µg purified rWNV-80E adjuvanted with Alum/CpG. WNV E-specific IgG was detected by enzyme-linked immunosorbent assay and neutralizing antibodies (nAbs) was detected using single-round infectious particles of WNV. Furthermore, T cell immunity was detected by enzyme-linked immunospot assay and intracellular cytokine staining assay. Notably, rWNV-80E was highly immunogenic and elicited potent humoral and cell immunity, as evidenced by significant levels of IFN-γ and TNF-α secretion in the T cells of mice. In summary, the Alum/CpG-adjuvanted rWNV-80E subunit vaccine elicited potent and balanced B- and T-cell immunity in mice, and therefore it is a promising candidate vaccine that warrants further investigation for use in human or veterinary applications.

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来源期刊
Biosafety and Health
Biosafety and Health Medicine-Infectious Diseases
CiteScore
7.60
自引率
0.00%
发文量
116
审稿时长
66 days
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