Posted in Resource, shingles vaccine

Metabolic Phenotypes Of Response to Vaccination in Humans

Metabolic responses to Zostavax vaccines over time (days 1, 3, 7). Source: Li et al., Cell, 2018

Zostavax is a licensed live-attenuated vaccine for prevention of HZ (shingles) in individuals aged 50 and above. HZ is caused by varicella zoster virus (VZV) reactivation, and Zostavax has been previously shown to confer ~50% reduction in HZ. Interestingly, the efficacy against HZ was 63.9% in subjects who were 60–69 years old but only 37.6% in subjects older than 70 years. In this article published in Cell, Li et al investigates why the efficacy of Zostavax could be different in the young and old subjects, using a multi-omics approach. Main findings are summarised below:

77 participants enrolled. 33 were young adults between the ages of 25 and 40 years and 44 were older subjects between the ages of 60 and 79 years.

PBMCs collected at baseline prior to vaccination and at days 1, 3, 7, 14, 28, 90, and 180 post-vaccination

Weak CD8+ T-cell responses seen in all subjects, but CD4 T-cell responses detected in the majority of subjects. Blood Tfh-like cells (CD4+CXCR5+CXCR3+ICOS+ T cells), known to be important in providing B-cell help, was also increased in both the young and elderly adults after vaccination.

The younger subjects had a greater increase of VZV-specific IgG antibody after vaccination compared to the elderly subjects.

Transcriptomics show increased interferon-stimulated genes at days 1 and 3, but the induction of these innate immune genes were of a smaller magnitude than the Yellow Fever live-attenuated vaccine. This is then followed by increased immunoglobulin transcripts at day 7. Of note, the increase in immunoglobulin genes coincided with the increase in antigen-specific plasmablast cells.

Comparing between young and elderly subjects, most differences were seen at baseline, including increased expression of genes in gene modules related to inflammation, cytosolic DNA sensing, and NK cells.

Among the different cell population phenotypes measured, day 7 IFN-γ+ T cells is the most significant predictor of IgG response. High activity in inositol phosphate metabolism is also associated with reduced T cell and B cell responses.

Sterol regulatory binding protein 1 and its targets is most predictive of Tfh response, IgG response, and the associations between genes and metabolite networks, including chemokine signaling (CCL23, CCL19, and CCR3), TNF/MAPK signaling (TNFSF11, VACM1, and DUSP6), complement genes (C1QA and C1QB), killer cell immunoglobulin-like receptors (KIR3DL3, KIR2DL3, and KIR2DS5), and lipid metabolic enzymes (ACSM2A, ACSM2B, and DGAT2).

Data is available at GEO: GSE79396

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