Live attenuated YFV-17D vaccine induces robust B and T cell immunity in vaccine-draining lymph nodes

Abstract

The yellow fever virus-17D (YFV-17D) vaccine is widely regarded as one of the most effective vaccines in existence, with protection linked to robust elicitation of neutralising antibodies1. The features of the germinal centre (GC) reaction driving this durable and potent antibody responses remain unclear. Here we examined immune dynamics in blood and lymph nodes (LNs) after primary YFV-17D immunisation in humans. Using fine needle biopsy (FNB), we identified robust T and B lymphocyte responses within draining LNs, underpinning maturation of antibodies targeting the viral envelope (E). Early antibody responses were largely IgM, with gradual accumulation of E-specific memory B cells and anti-viral IgG in the subsequent months. Monoclonal antibodies derived from GC B cells had specificity for E, with diversification in the LN capable of driving increases in binding and neutralising potency. While circulating vaccine-specific CD4+ T cells peaked two weeks post-vaccination, clonally related GC and IL-10+ T follicular helper populations progressively accumulated in the LN. Comparison of FNB transcriptional datasets following YFV-17D, SARS-CoV-2 mRNA/LNP, and seasonal influenza vaccination identified a conserved GC program involving similar B and T lymphocyte subpopulations. Collectively, we find that while YFV-17D induces robust GC activity, this trait is shared with other vaccine platforms and the notably durable protection against infection may reflect an incapacity of the virus to escape host immunity.

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BibTeX

@misc{evans2026live,
  title = {{Live attenuated YFV-17D vaccine induces robust B and T cell immunity in vaccine-draining lymph nodes}},
  author = {R. B. Evans and W. S. Lee and P. Mehta and C. A. Gonelli and M. Z. M. Zheng and R. Esterbauer and E. Reilly and K. M. Wragg and A. Kelly and J. J. Zaunders and T. G. Phan and S. Bibby and N. Modhiran and D. Watterson and S. Obeid and B. Milner and S. J. Kent and A. D. Kelleher and C. M. L. Munier and J. A. Juno and A. K. Wheatley},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.04.764404},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.04.764404v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Live attenuated YFV-17D vaccine induces robust B and T cell immunity in vaccine-draining lymph nodes
AU  - R. B. Evans
AU  - W. S. Lee
AU  - P. Mehta
AU  - C. A. Gonelli
AU  - M. Z. M. Zheng
AU  - R. Esterbauer
AU  - E. Reilly
AU  - K. M. Wragg
AU  - A. Kelly
AU  - J. J. Zaunders
AU  - T. G. Phan
AU  - S. Bibby
AU  - N. Modhiran
AU  - D. Watterson
AU  - S. Obeid
AU  - B. Milner
AU  - S. J. Kent
AU  - A. D. Kelleher
AU  - C. M. L. Munier
AU  - J. A. Juno
AU  - A. K. Wheatley
PY  - 2026
DA  - 2026/11/04
PB  - bioRxiv
DO  - 10.64898/2026.11.04.764404
UR  - https://www.biorxiv.org/content/10.64898/2026.11.04.764404v1
AB  - The yellow fever virus-17D (YFV-17D) vaccine is widely regarded as one of the most effective vaccines in existence, with protection linked to robust elicitation of neutralising antibodies1. The features of the germinal centre (GC) reaction driving this durable and potent antibody responses remain unclear. Here we examined immune dynamics in blood and lymph nodes (LNs) after primary YFV-17D immunisation in humans. Using fine needle biopsy (FNB), we identified robust T and B lymphocyte responses within draining LNs, underpinning maturation of antibodies targeting the viral envelope (E). Early antibody responses were largely IgM, with gradual accumulation of E-specific memory B cells and anti-viral IgG in the subsequent months. Monoclonal antibodies derived from GC B cells had specificity for E, with diversification in the LN capable of driving increases in binding and neutralising potency. While circulating vaccine-specific CD4+ T cells peaked two weeks post-vaccination, clonally related GC and IL-10+ T follicular helper populations progressively accumulated in the LN. Comparison of FNB transcriptional datasets following YFV-17D, SARS-CoV-2 mRNA/LNP, and seasonal influenza vaccination identified a conserved GC program involving similar B and T lymphocyte subpopulations. Collectively, we find that while YFV-17D induces robust GC activity, this trait is shared with other vaccine platforms and the notably durable protection against infection may reflect an incapacity of the virus to escape host immunity.
ER  -

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