Balancing neutralization and tolerance: spike-specific antibodies responses to repeated COVID-19 mRNA vaccine boosters in solid cancer patients

Background: Solid cancer patients are at increased risk of severe COVID-19 and may benefit from repeated booster doses of SARS-CoV-2 mRNA vaccines. Beyond neutralizing antibody titers, recent evidence highlights the induction of spike-specific IgG4 after multiple vaccine doses, a phenomenon potentially linked to immune tolerance. Methods: We investigated the humoral response following the administration of the fourth and fifth dose of the Comirnaty Omicron XBB.1.5 mRNA vaccine in 48 patients with solid tumors undergoing active or recent anticancer treatment, compared with age-matched controls (n=24). Serum samples were collected before (T1) and three weeks after vaccination (T2). IgG against the spike receptor-binding-domain (IgG-RBD-S), spike-specific IgM (IgM-S), and IgG4 (IgG4-S) were quantified using standardized assays.