Kinetic patterns of single cell gene expression discriminate between the murine cellular responses to live attenuated and inactivated Yellow Fever vaccines
Chatterjee, B.; Boughter, C. T.; Gorga, K.; Ohta, Y.; Blair, C.; Hill, E. M.; Fasana, Z.; Atuheirwe, M.; Adebamowo, A.; Ammar, F.; Ayithan, N.; Courneya, J.; Kosik, I.; Murugan, V.; Chen, W. H.; Pasetti, M. F.; Meier-Schellersheim, M.; Singh, N. J.
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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, but less effective version (InYF). Within the first week, we identify 70 kinetic patterns in 45 cellular clusters, majority of which discriminate between the two formulations, some in a tissue and sex-specific manner. Intriguingly, differential transcripts fall into two categories, one whose association with YF17D or InYF is maintained even when decoupled from their cell-type of expression and the other where such cell-plus-gene pairing is critical to maintain differential marker status. We demonstrate applications of this resource, by identifying B cells with varied interferon and antigen responsiveness in relation to each vaccine. This high-resolution dataset is amenable to further biomarker discovery and hypothesis generation.
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