Predictive signatures of immune response to vaccination and implications of the immune setpoint remodeling

In 2020, I featured two articles in the "mSphere of Influence"commentary series that had profound implications for the fieldof immunology and helped shape my research perspective. These articles were "Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses"by Tsang et al. (Cell 157:499-513, 2014, https://doi.org/10.1016/j.cell.2014.03.031) and "A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection"by Fourati et al. (Nat Commun 9:4418, 2018, https://doi.org/10.1038/s41467-018-06735-8). From these topics, the identificationof signatures predictive of immune responses to vaccination has greatly advanced and pivoted our understanding of how the immune state at the time of vaccination predicts (and potentially determines) vaccination outcomes. While most of this work has been done using influenzavaccination as a model, pan-vaccine signatures have been also identified.The key implications are their potential use to predict who will respond to vaccinations and to inform strategies for fine-tuningthe immune setpoint to enhance immune responses. In addition, investigations in this area led us to understand that immune perturbations, such as acute infections and vaccinations, can remodel the baseline immune state and alter immune responses to future exposures, expanding this exciting fieldof research. These processes are likely epigenetically encoded, and some examples have already been identifiedand are discussed in this minireview. Therefore, further research is essential to gain a deeper understanding of how immune exposures modify the epigenome and transcriptome, influencethe immune setpoint in response to vaccination, and defineits exposure-specificcharacteristics.