Early regional lymph node activation drives influenza vaccine responses in an ancestrally diverse cohort

Siu, J. H.; Coelho, S.; Palomeras, A.; Belij-Rammerstorfer, S.; Lee, C. H.; Strobel, T.; Thorpe, C.; Kaur, C.; Cole, T.; Remmert, N.; Fowler, J.; Pledger, S.; Dooley, K. B.; Opoka, D.; Szommer, T.; Vanderslott, S.; Kaleebu, P.; Milicic, A.; Palmer, D. B.; Lambe, T.; Marsden, B. D.; Koohey, H.; Coles, M.; Dendrou, C. A.; Pollock, K. M.

doi:10.1101/2024.10.28.620725

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bioRxiv · 10.1101/2024.10.28.620725

Early regional lymph node activation drives influenza vaccine responses in an ancestrally diverse cohort

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Abstract

Early in vivo dynamics of human immune-cell activation across regionally activated lymphoid tissue sites upon immunisation are poorly characterised in ancestrally diverse individuals. Here, we profiled draining and non-draining axillary lymph nodes (dLNs and ndLNs) by ultrasound-guided fine-needle aspiration (FNA) in 13 Black and Asian ancestry individuals, before and 3-7 days after vaccination with adjuvanted influenza vaccine. Draining but not ndLNs rapidly increased in size post-vaccination, by day 3, with distinct cellular dynamics determined through single cell multiomics. Dissecting LN cellular diversity into 42 lymphoid and non-lymphoid cell states, post-vaccination cell abundance changes were observed across all LNs, but dLNs were specifically characterised by CD4+ T follicular helper (CD4+ Tfh) cell expansion. Gene expression analysis revealed a dLN post-vaccination hub of multicellular activity defined by CD4+ Tfh signalling, cross-compartmental activation, translation, and enhanced antigen-presentation capacity. Thus, robust responses to intramuscular immunisation transcending ancestral inter-individual variation are elicited through temporal, anatomical and cellular lymphatic co-ordination with implications for vaccine design in ancestrally diverse populations. SummaryIn this study of ancestrally diverse young adults, the temporarily co-ordinated response to an adjuvanted influenza vaccine at lymph nodes local to (draining) and distal from (non-draining) the injection site, reveals early regulation of cellular kinetics and anatomical hierarchy of the innate and adaptive immune responses.

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Siu, J. H., Coelho, S., Palomeras, A., Belij-Rammerstorfer, S., Lee, C. H., Strobel, T., Thorpe, C., Kaur, C., Cole, T., Remmert, N., Fowler, J., Pledger, S., Dooley, K. B., Opoka, D., Szommer, T., Vanderslott, S., Kaleebu, P., Milicic, A., Palmer, D. B., Lambe, T., Marsden, B. D., Koohey, H., Coles, M., Dendrou, C. A., Pollock, K. M.. 2024-11-02. Early regional lymph node activation drives influenza vaccine responses in an ancestrally diverse cohort. https://doi.org/10.1101/2024.10.28.620725

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