ABSTRACT
Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here we investigated responses to COVID-19 mRNA vaccination via ultra-low-volume sampling and high-temporal-resolution transcriptome profiling (23 subjects across 22 timepoints, and with 117 COVID-19 patients used as comparators). There were marked differences in the timing and amplitude of the responses to the priming and booster doses. Notably, we identified two distinct interferon signatures. The first signature (A28/S1) was robustly induced both post-prime and post-boost and in both cases correlated with the subsequent development of antibody responses. In contrast, the second interferon signature (A28/S2) was robustly induced only post-boost, where it coincided with a transient inflammation peak. In COVID19 patients, a distinct phenotype dominated by A28/S2 was associated with longer duration of intensive care. In summary, high-temporal-resolution transcriptomic permitted the identification of post- vaccination phenotypes that are determinants of the course of COVID-19 disease.
Competing Interest Statement
D.R.G. outside of this work, reports investigator-initiated grants from Gilead Italia and Pfizer Inc. M.Ba Outside of this work work, reports research grants and/or advisor/consultant and/or Speaker/chairman Bayer, Biomerieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Shionogi. The other authors have no competing interests to report.
Footnotes
Writing has been improved throughout and a new analysis has been added to document the prevalence of Interferon Response Transcriptional Phenotypes (IRTPs) across several reference cohorts (Figure 8C).
