# PERSISTENCE OF PROTECTION CONFERRED BY SHINGRIX AGAINST HERPES ZOSTER IN OLDER ADULTS

> **NIH NIH U01** · UNIVERSITY OF COLORADO DENVER · 2020 · $715,495

## Abstract

Summary
 Herpes zoster (HZ) is the consequence of the reactivation of varicella-zoster virus (VZV), latent in
sensory neurons, that is not adequately controlled by ambient VZV-specific T cell immunity. These critical
immune responses decline with age. Of the two available HZ vaccines, one (Zostavax; zoster vaccine live
[ZVL]) is moderately efficacious (~50%), but efficacy is greatly influenced by the age of the vaccinee and
efficacy wanes at 5-8 years; the other vaccine (Shingrix; adjuvanted recombinant glycoprotein E vaccine
[SRX]) is ~90% effective, regardless of age at the time of administration, and to date has not waned.
 This proposal will define important differences in the immune response to each of the vaccines, and will
investigate mechanisms that explain these differences. We are able to recruit participants who received each
of these vaccines at least 5 years previously or in the past year, thus facilitating research on the difference in
durability of the two vaccines. As a model of reactivation of VZV, we will challenge participants (note: humans
are the only hosts in which VZV can be reliably studied) with intradermal VZV (the licensed vOka vaccine
strain) and use as an outcome measure the presence of VZV nucleic acids in blood, which we previously
showed occurred frequently after administration of this strain. This measure of viremia will be correlated with
measures of VZV-specific immune responses that limit the replication of the live VZV challenge virus. These
will include: 1) measures of local tissue (skin biopsy) responses using tissue imaging to detect VZV and the
nature of the early infiltrating immune cell types; 2) early plasma and tissue biomarkers (cytokines and
chemokines); 3) the phenotype of cell-mediated responses (T cells, NK, and antigen-presenting cell subsets);
4) transcriptomic analysis of early gene responses in skin and PBMC after the VZV challenge. This will be
aided by our finding gE-specific epitopes for HLA class I and II alleles that will be used to prepare gE-specific
tetramers.
 We will identify the components of the immune response to VZV challenge that are most likely to
mediate the control of viral replication. We are interested in systemic markers, since blood is readily accessible
and we seek immune correlates with control of viral replication that can be used in other studies. We are
including local responses, because rapidity and success of immune control of viral replication at the site of
inoculation (modelling the site of early replication of reactivated VZV) is crucial for HZ pathogenesis and
vaccine-conferred protection.
 The last aim of this application is to analyze the relationship of the responses to SRX administration
with the immune responses that reduce viremia after VZV challenge, especially the relationship between the
magnitude of gE-memory T cell responses to SRX (which we previously showed was a marker of this superior
HZ vaccine) and reduced viremia after VZV challenge.

## Key facts

- **NIH application ID:** 9886187
- **Project number:** 5U01AI141919-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** MYRON J LEVIN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $715,495
- **Award type:** 5
- **Project period:** 2019-03-06 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886187

## Citation

> US National Institutes of Health, RePORTER application 9886187, PERSISTENCE OF PROTECTION CONFERRED BY SHINGRIX AGAINST HERPES ZOSTER IN OLDER ADULTS (5U01AI141919-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886187. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*