Evolution of SARS-CoV-2 antibody repertoire after successive mRNA vaccinations under immunosuppressive treatment.

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2025-02-25 DOI:10.1016/j.ebiom.2025.105620

Jim B D Keijser, Eileen W Stalman, Luuk Wieske, Maurice Steenhuis, Koos P J van Dam, Laura Y L Kummer, Zoé L E van Kempen, Joep Killestein, Adriaan G Volkers, Sander W Tas, Laura Boekel, Gerrit J Wolbink, Laura Fernandez Blanco, Niels J M Verstegen, Sofie Keijzer, Gerard van Mierlo, Olvi Cristianawati, Arend J Boogaard, Karlijn van der Straten, Jacqueline van Rijswijk, Marit J van Gils, Anja Ten Brinke, S Marieke van Ham, Taco W Kuijpers, Filip Eftimov, Theo Rispens

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引用次数: 0

Abstract

Background: Repeated antigen exposure can result in a shifting antibody repertoire. The mechanisms by which this occurs and consequences for cross-variant protection against evolving pathogens remain incompletely understood, particularly in the context of immunosuppressive treatments used in patients with immune-mediated inflammatory diseases (IMID).

Methods: To investigate this, we characterised longitudinal changes in the anti-SARS-CoV-2 antibody repertoire over the course of three SARS-CoV-2 mRNA vaccinations in patients with IMIDs treated with methotrexate (MTX) and/or tumour necrosis factor-inhibitors (TNFi), anti-CD20 monoclonal antibodies, no systemic therapy, and healthy controls (total N = 878). We determined serum antibody titres against the receptor-binding domain (RBD) of Wuhan-Hu-1 (WH1) and Omicron BA.1 spike proteins, and assessed ratios thereof between groups as a proxy for cross-reactivity.

Findings: We observe emerging anti-BA.1 RBD reactivity over time, notably following a third vaccination. This may be partly explained by affinity maturation, as evaluated by inhibition of ACE2-RBD interactions. Similar trends were seen in patients treated with MTX and/or TNFi, but not in patients on anti-CD20 therapy. SARS-CoV-2 infection prior to vaccination accelerated these effects initially while leading to comparable results after three vaccinations.

Interpretation: MTX and TNFi do not qualitatively alter the evolution of the antibody repertoire in response to repeated antigen exposure, whereas anti-CD20 does. These insights may help to optimise vaccination strategies for patients with immune-mediated inflammatory diseases.

Funding: This study was supported by ZonMw (The Netherlands Organization for Health Research and Development) and SGF (Collaborating Health Funds).

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.