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

9 Citations (Scopus)
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Abstract

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 sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. Methods: In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2–specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination. Results: Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response. Conclusions: COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious 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
Volume149
Issue number6
DOIs
Publication statusPublished - 1 Jun 2022

Bibliographical note

Funding Information:
Disclosure of potential conflict of interest: M. J. van Gils received funding from the Amsterdam UMC Fellowship to support her research activities. J. Potjewijd received a grant from GlaxoSmithKline (GSK) for an improvement of clinical care project, received support from Prothva Biosolutions for attending meetings and cover of travel expenses, and participates in an Advisory Board for Janssen. A. A. J. M. van de Ven received a grant of the Stichting voor Afweerstoornissen (SAS, Dutch Patients Organization for inborn errors of immunity) and lecture honoraria from Takeda Pharmaceutical Company. S. F. J. de Kruijf-Bazen reported honoraria for lectures and support for attending meetings and/or travel from Takeda Pharmaceutical Company and participated in an advisory board for Takeda Pharmaceutical Company. F. van de Veerdonk received a grant from ZonMW for a study on lanadelumab in COVID-19, and consulting fees from GSK made to his department. H. L. Leavis received a Takeda Pharmaceutical Company research grant and consulting fees from Takeda Pharmaceutical Company made to her institution. P. M. van Hagen is cochair of the medical board of the International Patients Organisation for Primary Immunodeficiencies. V. A. S. H. Dalm received consulting fees from GSK for Advisory board meetings and honoraria for lectures from Takeda Pharmaceutical Company. The rest of the authors declare that they have no relevant conflicts of interest.

Funding Information:
This study was funded by ZonMw (grant no. 10430072010006 ), EudraCT number 2021-000515-24.

Publisher Copyright:
© 2022 The Authors

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