State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China.
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China.
Viruses. 2022 Aug 16;14(8):1785. doi: 10.3390/v14081785.
Varicella-zoster virus (VZV) is the causative agent of varicella and herpes zoster (HZ) and can pose a significant challenge to human health globally. The initial VZV infection-more common in children-causes a self-limiting chicken pox. However, in later life, the latent VZV can become reactivated in these patients, causing HZ and postherpetic neuralgia (PHN), a serious and painful complication. VZV glycoprotein E (gE) has been developed into a licensed subunit vaccine against HZ (Shingrix). However, its efficacy relies on the concomitant delivery of a robust adjuvant (AS01B). Here, we sought to create a new immunogen for vaccine design by displaying the VZV-gE on the baculovirus surface (Bac-gE). Correct localization and display of gE on the engineered baculovirus was verified by flow cytometry and immune electron microscopy. We show that Bac-gE provides excellent antigenicity against VZV and induces not only stronger gE-specific CD4 and CD8 T cell responses but also higher levels of VZV-specific neutralizing antibodies as compared with other vaccine strategies in mice. Collectively, we show that the baculovirus display of VZV-gE confers ideal humoral and cellular immune responses required for HZ vaccine development, paving the way for a baculovirus-based vaccine design.
水痘-带状疱疹病毒（VZV）是水痘和带状疱疹（HZ）的病原体，对全球人类健康构成重大挑战。初次 VZV 感染更常见于儿童，引起自限性水痘。然而，在以后的生活中，潜伏的 VZV 可在这些患者中重新激活，导致 HZ 和带状疱疹后神经痛（PHN），这是一种严重且疼痛的并发症。VZV 糖蛋白 E（gE）已被开发成一种针对 HZ 的许可亚单位疫苗（Shingrix）。然而，其疗效依赖于同时给予强大的佐剂（AS01B）。在这里，我们通过在杆状病毒表面展示 VZV-gE 来设计疫苗，试图创造一种新的免疫原。通过流式细胞术和免疫电子显微镜验证了 gE 在工程化杆状病毒上的正确定位和展示。我们表明，Bac-gE 对 VZV 具有极好的抗原性，不仅诱导更强的 gE 特异性 CD4 和 CD8 T 细胞反应，而且与小鼠中的其他疫苗策略相比，还诱导更高水平的 VZV 特异性中和抗体。总之，我们表明，VZV-gE 的杆状病毒展示赋予了 HZ 疫苗开发所需的理想体液和细胞免疫反应，为基于杆状病毒的疫苗设计铺平了道路。
