Chimeric adenovirus-based herpes zoster vaccine with the tPA signal peptide elicits a robust T-cell immune response

Abstract

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 × 107 IFU) elicited a more robust gE-specific T-cell response than Shingrix and Zostavax, showing potential as HZ prophylactic vaccines.