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一种展示寨卡病毒 prM-E 的细菌样颗粒疫苗可在小鼠中诱导全身性免疫应答。

A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice.

机构信息

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.

出版信息

Transbound Emerg Dis. 2022 Sep;69(5):e2516-e2529. doi: 10.1111/tbed.14594. Epub 2022 Jun 2.

Abstract

The emergence of Zika virus (ZIKV) infection, which is unexpectedly associated with congenital defects, has prompted the development of safe and effective vaccines. The Gram-positive enhancer matrix-protein anchor (GEM-PA) display system has emerged as a versatile and highly effective platform for delivering target proteins in vaccines. In this study, we developed a bacterium-like particle vaccine, ZI-△-PA-GEM, based on the GEM-PA system. The fusion protein ZI-△-PA, which contains the prM-E-△TM protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3, was expressed. The fusion protein was successfully displayed on the GEM surface to form ZI-△-PA-GEM. Moreover, the intramuscular immunization of BALB/c mice with ZI-△-PA-GEM combined with ISA 201 VG and poly(I:C) adjuvants induced durable ZIKV-specific IgG and protective neutralizing antibody responses. Potent B-cell/DC activation was also stimulated early after immunization. Notable, splenocyte proliferation, the secretion of multiple cytokines, T/B-cell activation and central memory T-cell responses were elicited. These data indicate that ZI-△-PA-GEM is a promising bacterium-like particle vaccine candidate for ZIKV.

摘要

寨卡病毒(ZIKV)感染的出现,出乎意料地与先天性缺陷有关,促使人们开发安全有效的疫苗。革兰氏阳性增强子基质蛋白锚(GEM-PA)展示系统已成为一种多功能且高效的平台,可在疫苗中输送靶向蛋白。在这项研究中,我们基于 GEM-PA 系统开发了一种类似细菌的颗粒疫苗 ZI-△-PA-GEM。融合蛋白 ZI-△-PA 包含 ZIKV 的 prM-E-△TM 蛋白(带有茎跨膜区缺失)和蛋白锚 PA3,被表达。融合蛋白成功地在 GEM 表面展示,形成 ZI-△-PA-GEM。此外,用 ZI-△-PA-GEM 联合 ISA 201 VG 和聚肌苷酸(poly(I:C))佐剂对 BALB/c 小鼠进行肌肉内免疫,诱导了持久的 ZIKV 特异性 IgG 和保护性中和抗体反应。免疫后早期还刺激了强烈的 B 细胞/DC 激活。值得注意的是,脾细胞增殖、多种细胞因子的分泌、T/B 细胞激活和中央记忆 T 细胞反应都被引发。这些数据表明 ZI-△-PA-GEM 是一种有前途的寨卡病毒类似细菌颗粒疫苗候选物。

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