Document Type
Article
Publication Date
12-1-2025
Original Citation
Johnson M,
Crotteau M,
Ghosh D,
Vu T,
Trinity L,
Marches R,
Ucar D,
Levin M,
Weinberg A.
The recombinant zoster vaccine induces trained immunity in monocytes through persistent downregulation of TGFβ. PLoS Pathog. 2025;21(12):e1013759.
Keywords
JGM, Humans, Monocytes, Herpes Zoster Vaccine, Vaccines, Synthetic, Herpesvirus 3, Human, Down-Regulation, Transforming Growth Factor beta1, Immunity, Innate, Transforming Growth Factor beta, Herpes Zoster, Female, Dendritic Cells, Male, Killer Cells, Natural, Trained Immunity
JAX Source
PLoS Pathog. 2025;21(12):e1013759.
ISSN
1553-7374
PMID
41348857
DOI
https://doi.org/10.1371/journal.ppat.1013759
Abstract
Older adults have decreased vaccine efficacy, but the adjuvanted recombinant VZV-gE zoster vaccine (RZV) is highly efficacious. We investigated memory-like innate immune responses after RZV and after the zoster vaccine live (ZVL), which is much less efficacious. RZV increased NK, monocyte, and DC activation in response to in vitro VZV-gE stimulation for up to 5 years post-vaccination, while ZVL increased only DC responses to VZV for up to 90 days. In purified monocyte and NK cell cocultures, RZV recipients showed increased responses to VZV-gE, HCMV and HSV antigenic stimulation post-vaccination. ATAC-seq analysis of purified monocytes revealed decreased accessibility in areas of the TGFβ1 gene. scRNA-seq and immunoproteomics confirmed decreased TGFβ1 transcription and translation, respectively. Exogenous supplementation and inhibition of TGFβ1 modulated in vitro monocyte responses to VZV-gE. In conclusion, RZV generated homologous (VZV-gE) and heterologous (HCMV, HSV) trained immunity in monocytes through genomic repression of the regulatory cytokine TGFβ-1. Cytokine modulation may represent a novel mechanism of generating trained immunity in myeloid cells.
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This work is licensed under a Creative Commons Attribution 4.0 International License.