Transcriptomic responses to YF17D and inactive YF

The success of the live attenuated Yellow Fever vaccine (YF17D) that elicits immunity lasting over thirty years has made it a widely used model to understand the generation of durable protection. We compare the early single-cell level transcriptional response in mice to YF17D and an adjuvanted-inactivated version (InYF). Within the first week, we identify over 70 kinetic patterns of transcripts in 45 cellular clusters, majority of which discriminate between the two formulations, including in a tissue and sex-specific manner. We delineate two categories of transcripts, one whose association with the YF17D or InYF is maintained even when decoupled from the cell-type of expression and the other where such pairing is critical to maintain differential marker status. We validate the utility of this extensive resource, identifying B cell clusters varying in interferon and antigen responsiveness in relation to each vaccine. The dataset is amenable to further biomarker discovery and hypothesis generation.