Characterization of Varicella-Zoster virus-specific T cell responses induced by viral reactivation or vaccination

Abstract

the responses by vaccination in mice and the responses by VZV reactivation in HZ patients. I evaluated the immunogenicity of a newly formulated gE protein-based HZ vaccine containing Second-generation Lipid Adjuvant (SLA), a synthetic TLR4 ligand, formulated in an oil-in-water emulsion (SLA-SE) without QS21 (gE/SLA-SE). In VZV-primed mouse models, gE/SLA-SE induced gE-specific humoral and cellular immune responses at comparable levels to those elicited by Shingrix in young mice, as both gE/SLA-SE and Shingrix induce polyfunctional CD4+ T-cell responses. In aged mice, gE/SLA-SE elicited more robust gE-specific T-cell responses than Shingrix. Furthermore, gE/SLA-SE-induced T-cell responses were sustained until 5 months after immunization. Thus, QS21-free, gE/SLA-SE is a promising candidate for development of gE-based HZ vaccines with high immunogenicity - particularly when targeting an older population. In HZ patients, VZV-specific T-cell responses were increased which is slightly associated with VZV DNA viral load. In addition, the frequency of VZV-specific CD8+ T cells was increased in day 28 with increased proportion of effector memory T cells. VZV-specific CD8+ T cells exhibited decreased expression of both activation markers and T cell inhibitory markers in day 28, and showed increased expression of CD57. Collectively, these result indicates that HZ reactivation resulted in the activation of VZV-specific CD8+ T cells, and the activated CD8+ T cells differentiated into effector memory T cells.

Herpes zoster (HZ) is caused by reactivation of latent varicella-zoster virus (VZV) when VZV-specific cellular immunity is insufficient to control reactivation. In this study, VZV-specific T-cell responses were characterized in two aspects