@article{Purcell_R-2025_214055,
title = {Dysregulated inflammation in solid tumor malignancy patients shapes polyfunctional antibody responses to COVID-19 vaccination},
author = {Purcell, R. and Koutsakos, M. and Kedzierski, L. and Allen, L. and Lloyd Williams, O. and Wang, J. and Cavic, G. and Wheatley, A. and Lee, W. and Wines, B. and Mark Hogarth, P. and Eriksson, E. and Mueller, I. and Bond, K. and Williamson, D. and Trevillyan, J. and Trubiano, J. and Ramanathan, P. and Rogerson, S. and Arnold, K. and Subbarao, K. and Lee, A. and Hudson, A. and Yuile, A. and Wheeler, H. and Kent, S. and Selva, K. and Mahanty, S. and Kedzierska, K. and Fahrer, A. and Kanjanapan, Y. and Chung, A. and Nguyen, T.},
month = {oct},
year = {2025},
abstract = {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.},
volume = {10},
journal = {npj Vaccines},
publisher = {Springer Nature},
url = {https://doi.org/10.1038/s41541-025-01268-w},
}
