Human Immune Responses to Different Covid-19 Vaccines

mRNA vaccines, administered in two doses, have been highly effective against SARS-CoV-2 and are now being explored for broader applications. However, how human immune cells respond to these platforms, particularly differences between primary and booster responses, remains incompletely understood. Here, we longitudinally profiled plasma and peripheral blood mononuclear cells from individuals without prior infection or vaccination receiving BNT162b2 (Pfizer, n=22), mRNA-1273 (Moderna, n=6), or the adenoviral vector vaccine Ad26.COV2.S (J&J, n=3). Using DOGMA-seq, a single-cell assay integrating transcriptomic and epigenomic profiling, we show that while the most robust responses occurred after the second dose, the first mRNA dose induces a unique interferon state in a subset of monocytes and dendritic cells.