A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice
A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice
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DOI：
10.1111/tbed.14594
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发表时间：
2022-06-02
影响因子：
4.3
通讯作者：
Wang, Hualei
中科院分区：
文献类型：
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作者：
Jin, Hongli;Bai, Yujie;Wang, Hualei
寨卡病毒(ZIKV)感染的出现，出人意料地与先天性缺陷有关，促使安全有效的疫苗的开发。革兰氏阳性增强子基质-蛋白锚(GEM-PA)展示系统已成为疫苗中传递靶蛋白的通用和高效平台。在本研究中，我们在GEM-PA系统的基础上开发了细菌样颗粒疫苗Zi-Delta-PA-GEM。表达了含有ZIKV PRM-E-Delta TM蛋白(茎-跨膜区缺失)和蛋白锚PA3的融合蛋白Zi-Delta-PA。融合蛋白成功地展示在宝石表面，形成Zi-Delta-PA-GEM。此外，Zi-Delta-PA-GEM联合ISA 201 VG和Poly(I：C)佐剂肌肉免疫BALB/c小鼠可诱导持久的ZIKV特异性免疫球蛋白和保护性中和抗体应答。免疫后早期也刺激了B细胞/DC的激活。显著刺激脾细胞增殖、多种细胞因子分泌、T/B细胞活化和中枢记忆T细胞反应。这些数据表明Zi-Delta-PA-GEM是一种很有前途的ZIKV细菌样颗粒疫苗候选疫苗。
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-Delta-PA-GEM, based on the GEM-PA system. The fusion protein ZI-Delta-PA, which contains the prM-E-Delta 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-Delta-PA-GEM. Moreover, the intramuscular immunization of BALB/c mice with ZI-Delta-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-Delta-PA-GEM is a promising bacterium-like particle vaccine candidate for ZIKV.