TY - JOUR
AU - Purcell, Ruth A.
AU - Koutsakos, Marios
AU - Kedzierski, Lukasz
AU - Allen, Lilith F.
AU - Lloyd Williams, Oscar H.
AU - Wang, Jo-Wai Douglas
AU - Cavic, George
AU - Wheatley, Adam K.
AU - Lee, Wen Shi
AU - Wines, Bruce D.
AU - Mark Hogarth, P.
AU - Eriksson, Emily M.
AU - Mueller, Ivo
AU - Bond, Katherine A.
AU - Williamson, Deborah A.
AU - Trevillyan, Janine M.
AU - Trubiano, Jason A.
AU - Ramanathan, Pradhipa
AU - Rogerson, Stephen J.
AU - Arnold, Kelly B.
AU - Subbarao, Kanta
AU - Lee, Adrian
AU - Hudson, Amanda L.
AU - Yuile, Alexander
AU - Wheeler, Helen R.
AU - Kent, Stephen J.
AU - Selva, Kevin John
AU - Mahanty, Siddhartha
AU - Kedzierska, Katherine
AU - Fahrer, Aude M.
AU - Kanjanapan, Yada
AU - Chung, Amy W.
AU - Nguyen, Thi Ho
PY - 2025
DA - October
TI - Dysregulated inflammation in solid tumor malignancy patients shapes polyfunctional antibody responses to COVID-19 vaccination
JO - npj Vaccines
VL - 10
DO - https://doi.org/10.1038/s41541-025-01268-w
AB - 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.
PB - Springer Nature
UR - https://hdl.handle.net/10023/32947
KW - Coronavirus (COVID-19)
KW - Immunisation and screening
ER