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<p>The degree to which COVID-19 vaccination induces B-cell responses in non-draining lymph nodes (LNs) is unknown. Therefore, non-draining iliac LNs and paired peripheral blood (PB) of end-stage renal disease patients were retrieved during kidney transplantation. Prior, participants received two (<i>n</i> = 5), three (<i>n</i> = 4), or four mRNA-based vaccinations (<i>n</i> = 3) and 4 patients had previous SARS-CoV-2 infection, of whom 2 received two vaccinations. Samples were obtained on average 79 days post-vaccination and 162 days post-infection. Spike S1(S)-binding B-cells were detected in LNs and PB 210 and 243 days after vaccination and infection, respectively. These B-cells predominantly consisted of IgG-secreting plasmablasts. In serum, a decreased IgG1/IgG4 ratio upon repeated vaccination, coherent with high fractions of S-binding IgG4 in LNs, correlated with reduced Fc-mediated functionalities but not neutralization capacity. Thus, mRNA-based COVID-19 vaccination could induce a systemic and long-lived, highly functional virus-specific B-cell response. Understanding IgG4 skewing is important for future vaccination strategies, especially in immunocompromised populations.</p>

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SARS-CoV-2-specific B cell responses in non-draining lymph nodes and antibody functionalities in immunized end-stage renal disease patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Sophie C. Frölke,
  • Daryl Geers,
  • Kenney G. Amirkhan,
  • Danisha Sri Pathmarajah,
  • Nelly van der Bom-Baylon,
  • Mirza M. Idu,
  • Marit van Gils,
  • Mathieu Claireaux,
  • Suzanne E. Geerlings,
  • Theo Rispens,
  • Rory D. de Vries,
  • Rob van Binnendijk,
  • Ester B. M. Remmerswaal,
  • Michiel C. van Aalderen,
  • Frederike J. Bemelman

摘要

The degree to which COVID-19 vaccination induces B-cell responses in non-draining lymph nodes (LNs) is unknown. Therefore, non-draining iliac LNs and paired peripheral blood (PB) of end-stage renal disease patients were retrieved during kidney transplantation. Prior, participants received two (n = 5), three (n = 4), or four mRNA-based vaccinations (n = 3) and 4 patients had previous SARS-CoV-2 infection, of whom 2 received two vaccinations. Samples were obtained on average 79 days post-vaccination and 162 days post-infection. Spike S1(S)-binding B-cells were detected in LNs and PB 210 and 243 days after vaccination and infection, respectively. These B-cells predominantly consisted of IgG-secreting plasmablasts. In serum, a decreased IgG1/IgG4 ratio upon repeated vaccination, coherent with high fractions of S-binding IgG4 in LNs, correlated with reduced Fc-mediated functionalities but not neutralization capacity. Thus, mRNA-based COVID-19 vaccination could induce a systemic and long-lived, highly functional virus-specific B-cell response. Understanding IgG4 skewing is important for future vaccination strategies, especially in immunocompromised populations.