R&D Center, GeneMatrix, Inc., Seongnam-si, Gyeonggi-do, Republic of Korea.
R&D Center, GeneMatrix, Inc., Seongnam-si, Gyeonggi-do, Republic of Korea.
Virology. 2024 Dec;600:110243. doi: 10.1016/j.virol.2024.110243. Epub 2024 Sep 16.
Herpes zoster (HZ), or shingles, is caused by reactivation of the varicella-zoster virus (VZV), which remains latent in the sensory ganglia until immunity wanes with age. The representative HZ vaccine, Shingrix is efficacious but causes side effects due to vaccine adjuvants. Therefore, the development of highly efficacious vaccines with minimal side effects is required. We developed chimeric adenovirus vector (ChimAd)-based HZ vaccine candidates encoding the VZV glycoprotein E (gE). These candidates include ChimAd-tPAgE, in which the signal peptide is replaced with tissue plasminogen activator (tPA), and ChimAd-WTgE, which retains the original signal peptide. C57BL/6 mice were immunized with VZV-vaccine candidates, and cellular and humoral immune responses were evaluated using interferon-γ ELISPOT and ELISA. The ChimAd-based HZ vaccines induced high levels of gE-specific antibodies and cell-mediated immunity. ChimAd-tPAgE (optimal dose: 1 × 10 IFU) elicited a more robust gE-specific T-cell response than Shingrix and Zostavax, showing potential as HZ prophylactic vaccines.
带状疱疹（HZ），又称水痘带状疱疹，由水痘-带状疱疹病毒（VZV）再激活引起，该病毒潜伏在感觉神经节中，直至免疫力随年龄下降而减弱。代表性的 HZ 疫苗，Shingrix 是有效的，但由于疫苗佐剂会引起副作用。因此，需要开发具有最小副作用的高效疫苗。我们开发了基于嵌合腺病毒载体（ChimAd）的 HZ 疫苗候选物，编码 VZV 糖蛋白 E（gE）。这些候选物包括用组织型纤溶酶原激活剂（tPA）替代信号肽的 ChimAd-tPAgE，以及保留原始信号肽的 ChimAd-WTgE。用 VZV-疫苗候选物免疫 C57BL/6 小鼠，并通过干扰素-γ ELISPOT 和 ELISA 评估细胞和体液免疫反应。基于 ChimAd 的 HZ 疫苗诱导高水平的 gE 特异性抗体和细胞介导的免疫。ChimAd-tPAgE（最佳剂量：1×10 IFU）引起的 gE 特异性 T 细胞反应比 Shingrix 和 Zostavax 更强烈，显示出作为 HZ 预防性疫苗的潜力。
