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LZ901疫苗与HZ/su疫苗在小鼠模型中的免疫原性比较

Comparison of the Immunogenicity of the LZ901 Vaccine and HZ/su Vaccine in a Mouse Model.

作者信息

Quan Yaru, Liu Chunxia, Lu Xu, Kong Xi, Yang Shuai, Kong Jian, Wan Wenyan, Wang Kaiqin, Xu Kangwei, Peng Ling

机构信息

NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, National Institutes for Food and Drug Control, Beijing 102629, China.

Beijing Luzhu Biotechnology Co., Ltd., Beijing 101100, China.

出版信息

Vaccines (Basel). 2024 Jul 15;12(7):775. doi: 10.3390/vaccines12070775.

Abstract

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4 and CD8 T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice.

摘要

带状疱疹(HZ)是一种由水痘-带状疱疹病毒(VZV)再激活引起的传染病,68%的病例发生在50岁以上的成年人中。重组带状疱疹疫苗(HZ/su,商品名Shingrix)于2017年获得美国食品药品监督管理局批准,用于预防50岁及以上人群的HZ,并且显示出对HZ具有很好的保护作用。然而,由于使用了佐剂AS01,Shingrix引起的不良反应受到关注。氢氧化铝是最常用的佐剂,广泛应用于多种疫苗中。我们开发了一种重组带状疱疹疫苗(代号:LZ901),它由VZV糖蛋白E(gE)的四聚体和在CHO细胞中表达的人Fc融合蛋白组成,是一种可被氢氧化铝佐剂吸附的免疫复合物样分子。我们在BALB/c小鼠中比较了LZ901和HZ/su的免疫原性。结果显示,LZ901诱导的gE特异性IgG抗体水平与HZ/su诱导的相当,FAMA滴度结果进一步证明了它们相似的中和抗体能力。最重要的是,在BALB/c小鼠中,LZ901诱导的细胞介导免疫(CMI)(在带状疱疹疫苗的疗效中起决定性作用)水平高于HZ/su。接种LZ901的小鼠中产生细胞因子的T细胞数量显著多于接种疫苗的小鼠,接种LZ901的小鼠中产生至少两种细胞因子的CD4和CD8 T细胞比例显著高于接种HZ/su的小鼠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6327/11281325/807db1ca703e/vaccines-12-00775-g001.jpg

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