Experimental model of VZV reactivation reveals vaccine-induced mechanisms of protection against herpes zoster
- 1University of Colorado School of Medicine Anschutz Medical Campus
Abstract
Herpes zoster (HZ), caused by varicella zoster virus (VZV) reactivation, is common in older adults with declining cell-mediated immune protection. A modestly efficacious live attenuated (ZVL) and a highly efficacious recombinant adjuvanted (RZV) zoster vaccine protect against HZ. To uncover the mechanism(s) associated with the superior efficacy of RZV, we developed a controlled human infection model consisting of intradermal administration of attenuated vOka VZV to older adults previously vaccinated with RZV or ZVL. Infiltration of VZV-specific CD4+ and CD8+ T cell clonotypes at the infection site was quicker and higher in RZV than ZVL recipients [≥]5 years post-immunization due to the persistence of RZV-induced gE-reactive CD4+ and CD8+ T cell clonotypes in blood. High CD4+ cytotoxic T lymphocyte frequencies in blood on Day 1 post-inoculation predicted control of VZV replication. Persistence of circulating RZV-induced CD4+ and CD8+ CTL and rapid migration to sites of VZV replication are potential mechanisms underlying durable protection against HZ.
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BibTeX
@misc{johnson2026experimental,
title = {{Experimental model of VZV reactivation reveals vaccine-induced mechanisms of protection against herpes zoster}},
author = {M. J. Johnson and T. Vu and E. S. Ford and L. Jing and K. Jordan and M. Brown and S. Li and T. Schedin and M. Crotteau and J. Canniff and A. Bennett and N. Weaver and K. J. Laing and S. Frietze and D. M. Koelle and M. J. Levin and A. Weinberg},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.26363709},
url = {https://www.medrxiv.org/content/10.64898/2026.09.22.26363709v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Experimental model of VZV reactivation reveals vaccine-induced mechanisms of protection against herpes zoster
AU - M. J. Johnson
AU - T. Vu
AU - E. S. Ford
AU - L. Jing
AU - K. Jordan
AU - M. Brown
AU - S. Li
AU - T. Schedin
AU - M. Crotteau
AU - J. Canniff
AU - A. Bennett
AU - N. Weaver
AU - K. J. Laing
AU - S. Frietze
AU - D. M. Koelle
AU - M. J. Levin
AU - A. Weinberg
PY - 2026
DA - 2026/09/22
PB - medRxiv
DO - 10.64898/2026.09.22.26363709
UR - https://www.medrxiv.org/content/10.64898/2026.09.22.26363709v1
AB - Herpes zoster (HZ), caused by varicella zoster virus (VZV) reactivation, is common in older adults with declining cell-mediated immune protection. A modestly efficacious live attenuated (ZVL) and a highly efficacious recombinant adjuvanted (RZV) zoster vaccine protect against HZ. To uncover the mechanism(s) associated with the superior efficacy of RZV, we developed a controlled human infection model consisting of intradermal administration of attenuated vOka VZV to older adults previously vaccinated with RZV or ZVL. Infiltration of VZV-specific CD4+ and CD8+ T cell clonotypes at the infection site was quicker and higher in RZV than ZVL recipients [≥]5 years post-immunization due to the persistence of RZV-induced gE-reactive CD4+ and CD8+ T cell clonotypes in blood. High CD4+ cytotoxic T lymphocyte frequencies in blood on Day 1 post-inoculation predicted control of VZV replication. Persistence of circulating RZV-induced CD4+ and CD8+ CTL and rapid migration to sites of VZV replication are potential mechanisms underlying durable protection against HZ.
ER -