Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high–temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.

With the advent of genome-wide screening methods—beginning with microarray technologies and moving onto next generation sequencing methods—the era of precision and personalized medicine was born. Genomics led the way, and its contributions are well recognized. However, “other-omics” fields have rapidly emerged and are becoming as important toward defining disease causes and exploring therapeutic benefits. In this review, we focus on the impacts of transcriptomics, and its extension—epitranscriptomics—on personalized and precision medicine efforts. There has been an explosion of transcriptomic studies particularly in the last decade, along with a growing number of recent epitranscriptomic studies in several disease areas. Here, we summarize and overview major efforts for cancer, cardiovascular disease, and neurodevelopmental disorders (including autism spectrum disorder and intellectual disability) for transcriptomics/epitranscriptomics in precision and personalized medicine. We show that leading advances are being made in both diagnostics, and in investigative and landscaping disease pathophysiological studies. As transcriptomics/epitranscriptomics screens become more widespread, it is certain that they will yield vital and transformative precision and personalized medicine contributions in ways that will significantly further genomics gains.

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Knowledge of the factors contributing to the development of protective immunity after vaccination with COVID-19 mRNA vaccines is fragmentary. Thus we employed high-temporal-resolution transcriptome profiling and in-depth characterization of antibody production approaches to investigate responses to COVID-19 mRNA vaccination. There were marked differences in the timing and amplitude of the responses to the priming and booster doses. Notably, two distinct interferon signatures were identified, that differed based on their temporal patterns of induction. The first signature (S1), which was preferentially induced by type I interferon, peaked at day 2 post-prime and at day 1 post-boost, and in both instances was associated with subsequent development of the antibody response. In contrast, the second interferon signature (S2) peaked at day 1 both post-prime and post-boost but was found to be potently induced only post-boost, where it coincided with a robust inflammation peak. Notably, we also observed post-prime-like (S1++,S20/+) and post-boost-like (S1++,S2++) patterns of interferon response among COVID-19 patients. A post-boost-like signature was observed in most severely ill patients at admission to the intensive care unit and was associated with a shorter hospital stay. Interestingly, severely ill patients who stayed hospitalized the longest showed a peculiar pattern of interferon induction (S1-/0,S2+), that we did not observe following the administration of mRNA vaccines. In summary, high temporal resolution profiling revealed an elaborate array of immune responses elicited by priming and booster doses of COVID-19 mRNA vaccines. Furthermore, it contributed to the identification of distinct interferon-response phenotypes underpinning vaccine immunogenicity and the course of COVID-19 disease.