Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity

Leanne P M van Leeuwen, Corine H GeurtsvanKessel, Pauline M Ellerbroek, Godelieve J de Bree, Judith Potjewijd, Abraham Rutgers, Hetty Jolink, Frank van de Veerdonk, Eric C M van Gorp, Faye de Wilt, Susanne Bogers, Lennert Gommers, Daryl Geers, Anke H W Bruns, Helen L Leavis, Jelle W van Haga, Bregtje A Lemkes, Annelou van der Veen, S F J de Kruijf-Bazen, Pieter van PaassenKarina de Leeuw, Annick A J M van de Ven, Petra H Verbeek-Menken, Annelies van Wengen, Sandra M Arend, Anja J Ruten-Budde, Marianne W van der Ent, P Martin van Hagen, Rogier W Sanders, Marloes Grobben, Karlijn van der Straten, Judith A Burger, Meliawati Poniman, Stefan Nierkens, Marit J van Gils, Rory D de Vries, Virgil A S H Dalm*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients.

OBJECTIVES: We studied humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult IEI patients.

METHODS: In a prospective, controlled, multicenter study 505 IEI patients (common variable immunodeficiency (CVID), isolated or undefined antibody deficiencies, X-linked agammaglobulinemia (XLA), combined immunodeficiency (CID), phagocyte defects) and 192 controls were included. All participants received two doses of the mRNA-1273 COVID-19 vaccine. Levels of SARS-CoV-2-specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first and 28 days after second vaccination.

RESULTS: Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to healthy controls, but seroconversion rates in patients with more severe IEI, like CVID and CID, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to controls in all IEI cohorts, with the exception of CVID patients. The presence of non-infectious complications and the use of immunosuppressive drugs in CVID patients were negatively correlated with the antibody response.

CONCLUSION: COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with CID and CVID. Lowest response was detected in XLA and in CVID patients with non-infectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision-making for additional vaccinations.

Original languageEnglish
Pages (from-to)1949-1957
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Issue number6
Early online date11 Apr 2022
Publication statusPublished - Jun 2022


  • CID
  • CVID
  • Inborn errors of immunity
  • SARS-CoV-2
  • T-cell response
  • XLA
  • antibody response
  • immuno-genicity
  • mRNA-1273 COVID-19 vaccine
  • primary immunodeficiency disorders

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