Single-cell Multi-omics of the Immune Response to Vaccination
A recent viral study revealed that SARS-CoV-2 infection alters chromatin accessibility in our all-important immune cells to facilitate immune memory – but does the same apply to vaccination? To answer this somewhat flu-mmoxing question, a flu-id force of epigeneticists led by Bali Pulendran (Stanford University, California) utilized single-cell multi-omics to explore the effects of influenza vaccination in human immune cells.
The authors employed a combination of cytometry by time-of-flight (EpiTOF), single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq), and single-cell RNA sequencing (scRNA-seq) to evaluate epigenomic and transcriptional responses in immune cells from patients receiving seasonal and pandemic influenza vaccinations. Without getting themselves flu-stered, the team also evaluated the epigenetic impact of AS03, a vaccine adjuvant system that supports the production of elevated levels of antigen-specific antibodies.
Let’s hear what this soon-to-be-influenz-tial single-cell multi-omics study from Wimmers and colleagues discovered:
- Vaccination with a trivalent inactivated seasonal influenza vaccine induces global chromatin profile alterations in multiple immune cell subsets that peaks at three-to-four weeks but persists for up to six months
- Monocytes and myeloid dendritic cells exhibit an open-to-closed switch at AP-1 transcription factor-associated loci, which associates with a reduction in H3K27ac levels and PADI4 expression, an arginine deiminase that catalyzes histone citrullination
- Epigenetic alterations reduce cytokine production following stimulation of the innate immune response with viral factors
- Single-cell ATAC-seq analysis reveals that distinct subclusters of monocytes display significant differences in AP-1 accessibility, and hence immune functionality
- Vaccination with the AS03-adjuvanted H5N1 pre-pandemic influenza vaccine prompts similar long-lasting epigenetic effects (and functional consequences) in monocytes and myeloid dendritic cells
- The vaccine and adjuvant combo also increases chromatin accessibility at binding sites for the interferon-regulatory factors (IRFs) and signal transducer and activator of transcription (STAT) family of transcription factors, which are of importance in anti-viral immunity
- These changes support the elevated expression of anti-viral genes and interferon production as well as resistance to unrelated viruses (Zika and dengue) during in vitro culture
Far from flu-nking out, these researchers have described the epigenetic remodeling (and their functional consequences) in immune cells induced by influenza vaccination and highlighted AS03 as a potentially important epigenetic adjuvant that could help to provide pan-viral protection to at-risk populations. Overall, this single-cell multi-omics study suggests that we may be able to harness specific epigenetic alterations to widen anti-viral responses to protect against SARs-CoV-2.
To see how single-cell multi-omics established epigenetic alterations as a means to improve anti-viral responses, flu-tter over to Cell, June 2021.