Assessing chromatin accessibility in human classical monocytes following vaccination with mRNA and adenoviral vectored COVID-19 vaccines

An increasing body of literature suggests that innate immune cells such as monocytes undergo epigenetic reprogramming following challenges such as infection or vaccination. We performed omni-ATACseq to assess chromatin accessibility in classical monocytes (CD14+CD16-) isolated from healthy participants before vaccination or 28 days following the second dose of an mRNA or adenoviral vectored COVID-19 vaccine. SARS-CoV-2 naïve participants from the COVIR study in South Australia were immunised with two doses of either BNT162b2 ‘Comirnaty’ vaccine 3 weeks apart, or 2 doses of ChAdOx1-s ‘Vaxzevria’ 3 months apart. There are 82 samples from 41 individuals prior to vaccination (V0) or 28 days following the second dose of vaccine (V2B). Cryopreserved PBMC were thawed and stained and classical monocytes (CD3-CD19-CD56-CD14+CD16-; 50,000 per sample) were sorted via flow cytometry and used for transposition with Tn5 transposase (illumina). Libraries were prepared from transposed DNA with custom primers and subjected to double-sided cleanup with SPRI beads to enrich for fragments in the 200-700bp range. Samples were sequenced on an illumina NovaSeq using paired end (2x150pb) sequencing.