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

Purcell, RA; Koutsakos, M; Kedzierski, L; Allen, LF; Lloyd Williams, OH; Wang, JD; Cavic, G; Wheatley, AK; Lee, WS; Wines, BD; Hogarth, PM; Eriksson, EM; Mueller, I; Bond, KA; Williamson, DA; Trevillyan, JM; Trubiano, JA; Nguyen, THO; Ramanathan, P; Rogerson, SJ; Arnold, KB; Subbarao, K; Lee, A; Hudson, AL; Yuile, A; Wheeler, HR; Kent, SJ; Selva, KJ; Mahanty, S; Kedzierska, K; Fahrer, AM; Kanjanapan, Y; Chung, AW

Author(s): Purcell, RA; Koutsakos, M; Kedzierski, L; Allen, LF; Lloyd Williams, OH; Wang, JD; Cavic, G; Wheatley, AK; Lee, WS; Wines, BD; Hogarth, PM; Eriksson, EM; Mueller, I; Bond, KA; Williamson, DA; Trevillyan, JM; Trubiano, JA; Nguyen, THO; Ramanathan, P; Rogerson, SJ; Arnold, KB; Subbarao, K; Lee, A; Hudson, AL; Yuile, A; Wheeler, HR; Kent, SJ; Selva, KJ; Mahanty, S; Kedzierska, K; Fahrer, AM; Kanjanapan, Y; Chung, AW;
Details: Publication Year 2025-10-06,Volume 10,Issue #1,Page 217
Journal Title: NPJ Vaccines
Publication Type: Research article
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.
Publisher: Springer Nature
Department(s): Infectious Diseases
Publisher's Version: https://doi.org/10.1038/s41541-025-01268-w
Open Access at Publisher's Site: https://doi.org/10.1038/s41541-025-01268-w
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-11-18 06:08:09

Last Modified: 2025-11-18 06:08:17