ArticleScience advances2025
Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Immunological imprinting shapes the cross-reactive antibody responses to the KP.2 and LP.8.1 vaccine doses.Journal of virology · 2026Article
- Malaria serology for surveillance, insights into immunity, and vaccine development.Infection and immunity · 2026Review
- Simultaneous quantification of anti-Spike IgG subclasses against various SARS-CoV-2 variants using a multiplex serological assay.Medical microbiology and immunology · 2026Article
- Uptake of Shingles, Influenza, COVID-19 and Pneumococcal Vaccination in Patients with Inflammatory Arthritis: A Three-Centre Study.Vaccines · 2026Article
- Measuring Humoral Immune Responses to SARS-CoV-2: A Comprehensive Review of Serological Assays.Vaccines · 2026Review
- Building better antibody responses: The interplay of infection, vaccination, and immune imprinting.PNAS nexus · 2026Review
- IgG4 Neutralization and Sustained Total IgG Fc-Effector Functions Following Repeated SARS-CoV-2 Vaccination with mRNA-1273.Infectious diseases and therapy · 2026Article
- COVID-19 mRNA vaccines: a prospective outlook from technological innovation to clinical practice.Frontiers in immunology · 2026Review
- Fc effector functions in RNA viral infections: mechanisms of antiviral immunity and implications for vaccine design.Frontiers in immunology · 2026Review
- Dysregulated inflammation in solid tumor malignancy patients shapes polyfunctional antibody responses to COVID-19 vaccination.NPJ vaccines · 2025Article
- High Free IgE and Mast Cell Activation in Long COVID: Mechanisms of Persistent Immune Dysregulation.Life (Basel, Switzerland) · 2025Article
- Article
- The evolution of analytical techniques for multiplex analysis of protein biomarkers.Expert review of proteomics · 2025Review
- Repeated COVID-19 Vaccination as a Poor Prognostic Factor in Pancreatic Cancer: A Retrospective, Single-Center Cohort Study.Cancers · 2025Article
- Variant-adapted COVID-19 vaccine boosters enhance humoral immunity and limit IgG4 accumulation in solid cancer patients.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Repeated mRNA COVID-19 vaccination increases spike-specific immunoglobulin G4 (IgG4) titers. Here, we characterized the influence of increased IgG4 titers on a range of Fc-mediated responses. Elevated spike-specific IgG4 reduced binding to FcγRIIIa and decreased antibody-dependent cellular cytotoxicity. However, in individuals with lower total spike-specific IgG, IgG4 acted in synergy with other IgG subclasses to improve FcγRI and FcγRIIa binding and consequently antibody-dependent cellular phagocytosis. Furthermore, this trend was more pronounced with more recent SARS-CoV-2 variants where vaccination induced comparably lower total spike-specific titers. These observations were further confirmed by in silico modeling where antibody subclass concentrations and FcγR polymorphisms were modulated. Collectively, we illustrate that the impact of elevated IgG4 titers upon Fc functions is dependent on multiple interconnected antibody and antigen factors, which should be taken into consideration when dissecting the mechanisms driving an effective Fc-mediated response following vaccination.
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