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<p>Solid tumor malignancy (STM) patients experience increased risk of breakthrough SARS-CoV-2 infection owing to reduced COVID-19 vaccine immunogenicity. However, the underlying immunological causes of impaired neutralization remain poorly characterized. Furthermore, non-neutralizing antibody functions can contribute to reduced disease severity but remain understudied within high-risk populations. We dissected polyfunctional antibody responses in STM patients and age-matched controls who received adenoviral vector- or mRNA-based COVID-19 vaccine regimens. Elevated inflammatory biomarkers, including agalactosylated IgG, interleukin (IL)-6, IL-18, and an expanded population of CD11c<sup>−</sup>CD21<sup>−</sup> double negative 3 (DN3) B cells were observed in STM patients and were associated with impaired neutralization. In contrast, mRNA vaccination induced Fc effector functions that were comparable in patients and controls and were cross-reactive against SARS-CoV-2 variants. These data highlight the resilience of Fc functional antibodies and identify systemic inflammatory biomarkers that may underpin impaired neutralizing antibody responses, suggesting potential avenues for immunomodulation via rational vaccine design.</p>

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Dysregulated inflammation in solid tumor malignancy patients shapes polyfunctional antibody responses to COVID-19 vaccination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Ruth A. Purcell,
  • Marios Koutsakos,
  • Lukasz Kedzierski,
  • Lilith F. Allen,
  • Oscar H. Lloyd Williams,
  • Jo-Wai Douglas Wang,
  • George Cavic,
  • Adam K. Wheatley,
  • Wen Shi Lee,
  • Bruce D. Wines,
  • P. Mark Hogarth,
  • Emily M. Eriksson,
  • Ivo Mueller,
  • Katherine A. Bond,
  • Deborah A. Williamson,
  • Janine M. Trevillyan,
  • Jason A. Trubiano,
  • Thi H. O. Nguyen,
  • Pradhipa Ramanathan,
  • Stephen J. Rogerson,
  • Kelly B. Arnold,
  • Kanta Subbarao,
  • Adrian Lee,
  • Amanda L. Hudson,
  • Alexander Yuile,
  • Helen R. Wheeler,
  • Stephen J. Kent,
  • Kevin John Selva,
  • Siddhartha Mahanty,
  • Katherine Kedzierska,
  • Aude M. Fahrer,
  • Yada Kanjanapan,
  • Amy W. Chung

摘要

Solid tumor malignancy (STM) patients experience increased risk of breakthrough SARS-CoV-2 infection owing to reduced COVID-19 vaccine immunogenicity. However, the underlying immunological causes of impaired neutralization remain poorly characterized. Furthermore, non-neutralizing antibody functions can contribute to reduced disease severity but remain understudied within high-risk populations. We dissected polyfunctional antibody responses in STM patients and age-matched controls who received adenoviral vector- or mRNA-based COVID-19 vaccine regimens. Elevated inflammatory biomarkers, including agalactosylated IgG, interleukin (IL)-6, IL-18, and an expanded population of CD11c−CD21− double negative 3 (DN3) B cells were observed in STM patients and were associated with impaired neutralization. In contrast, mRNA vaccination induced Fc effector functions that were comparable in patients and controls and were cross-reactive against SARS-CoV-2 variants. These data highlight the resilience of Fc functional antibodies and identify systemic inflammatory biomarkers that may underpin impaired neutralizing antibody responses, suggesting potential avenues for immunomodulation via rational vaccine design.