Evidence map›Paper›PMID 40010153›Full record

ArticleEBioMedicine2025

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

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 and 17 more

Abstract read
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Jim B D KeijserDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Eileen W StalmanDepartment of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Luuk WieskeDepartment of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Clinical Neurophysiology, St Antonius Hospital, Nieuwegein, the Netherlands.
Maurice SteenhuisDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Koos P J van DamDepartment of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Laura Y L KummerDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Department of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Zoé L E van KempenDepartment of Neurology, Amsterdam UMC, Amsterdam, the Netherlands.
Joep KillesteinDepartment of Neurology, Amsterdam UMC, Amsterdam, the Netherlands.
Adriaan G VolkersDepartment of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Sander W TasAmsterdam Rheumatology and Immunology Center, Department of Rheumatology and Clinical Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Laura BoekelAmsterdam Rheumatology and Immunology Center, Department of Rheumatology, Reade, Amsterdam, the Netherlands.
Gerrit J WolbinkAmsterdam Rheumatology and Immunology Center, Department of Rheumatology, Reade, Amsterdam, the Netherlands.
Laura Fernandez BlancoDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Niels J M VerstegenDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Sofie KeijzerDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Gerard van MierloDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Olvi CristianawatiDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Arend J BoogaardDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Karlijn van der StratenAmsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Jacqueline van RijswijkAmsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Marit J van GilsAmsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Anja Ten BrinkeDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
S Marieke van HamDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.
Taco W KuijpersDepartment of Pediatric Immunology, Rheumatology and Infectious Disease, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Filip EftimovAmsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
Theo RispensDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands; Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Electronic address: t.rispens@sanquin.nl.
T2B! Immunity against SARS-CoV-2 study group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRepeated 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).

methodsTo 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.

findingsWe 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.

interpretationMTX 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.

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

Indexed as

Antibodies, ViralCOVID-19COVID-19 VaccinesImmunosuppressive AgentsSARS-CoV-2AdultAgedFemaleHumansMaleMethotrexateMiddle AgedmRNA VaccinesSpike Glycoprotein, CoronavirusVaccinationAntibodies, ViralCOVID-19 VaccinesImmunosuppressive AgentsMethotrexatemRNA VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Antibody repertoireAutoimmune diseasemRNA vaccinesSARS-CoV-2Serology

Identifiers

PMID40010153
PMCPMC11905820

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.