Baculovirus Display of Varicella-Zoster Virus Glycoprotein E Induces Robust Humoral and Cellular Immune Responses in Mice

杆状病毒表达水痘-带状疱疹病毒糖蛋白E可诱导小鼠产生强烈的体液和细胞免疫反应

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作者:Wenhui Xue ,Tingting Li ,Sibo Zhang ,Yingbin Wang ,Minqing Hong ,Lingyan Cui ,Hong Wang ,Yuyun Zhang ,Tingting Chen ,Rui Zhu ,Zhenqin Chen ,Lizhi Zhou ,Rongwei Zhang ,Tong Cheng ,Qingbing Zheng ,Jun Zhang ,Ying Gu ,Ningshao Xia ,Shaowei Li

Abstract

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.

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