Spatiotemporal Transcriptomic Immune Responses to a Recombinant Hemagglutinin Protein Vaccine [CosMx SMI profiling]

Here, we applied high-plex spatial transcriptomics to profile early responses to an adjuvanted recombinant haemagglutinin (rHA) protein vaccine. In mice, early innate activation was observed in non-follicular lymph node regions at Day 1, transitioning to adaptive, germinal centre–associated responses within follicles by Day 7.

At the injection site, stromal and muscle cells exhibited strong chemokine and interferon responses, spatially localised to fibroblast-rich regions. These tissue-level dynamics were accompanied by transient systemic cytokine responses and increased antigen-specific IgG. Together, this study links spatially organised local inflammation with lymph node architecture to define early vaccine-induced immune responses.