Immune Responses 6 Months After mRNA-1273 COVID-19 Vaccination and the Effect of a Third Vaccination in Patients with Inborn Errors of Immunity

Leanne P M van Leeuwen, Marloes Grobben, VACOPID Research Group, Corine H GeurtsvanKessel, Pauline M Ellerbroek, Godelieve J de Bree, Judith Potjewijd, Abraham Rutgers, Hetty Jolink, Frank L van de Veerdonk, Marit J van Gils, Rory D de Vries, Virgil A S H Dalm*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

PURPOSE: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective long-term protection against COVID-19 is therefore of great importance in these patients, but little is known about the decay of the immune response after primary vaccination. We studied the immune responses 6 months after two mRNA-1273 COVID-19 vaccines in 473 IEI patients and subsequently the response to a third mRNA COVID-19 vaccine in 50 patients with common variable immunodeficiency (CVID).

METHODS: In a prospective multicenter study, 473 IEI patients (including X-linked agammaglobulinemia (XLA) (N = 18), combined immunodeficiency (CID) (N = 22), CVID (N = 203), isolated or undefined antibody deficiencies (N = 204), and phagocyte defects (N = 16)), and 179 controls were included and followed up to 6 months after two doses of the mRNA-1273 COVID-19 vaccine. Additionally, samples were collected from 50 CVID patients who received a third vaccine 6 months after primary vaccination through the national vaccination program. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T cell responses were assessed.

RESULTS: At 6 months after vaccination, the geometric mean antibody titers (GMT) declined in both IEI patients and healthy controls, when compared to GMT 28 days after vaccination. The trajectory of this decline did not differ between controls and most IEI cohorts; however, antibody titers in CID, CVID, and isolated antibody deficiency patients more often dropped to below the responder cut-off compared to controls. Specific T cell responses were still detectable in 77% of controls and 68% of IEI patients at 6 months post vaccination. A third mRNA vaccine resulted in an antibody response in only two out of 30 CVID patients that did not seroconvert after two mRNA vaccines.

CONCLUSION: A similar decline in IgG titers and T cell responses was observed in patients with IEI when compared to healthy controls 6 months after mRNA-1273 COVID-19 vaccination. The limited beneficial benefit of a third mRNA COVID-19 vaccine in previous non-responder CVID patients implicates that other protective strategies are needed for these vulnerable patients.

Original languageEnglish
Pages (from-to)1104-1117
Number of pages14
JournalJournal of Clinical Immunology
Volume43
Issue number6
Early online date26 May 2023
DOIs
Publication statusPublished - Aug 2023

Bibliographical note

Funding Information:
VACOPID Research Group Collaborators Eric C.M. van Gorp1,2MD PhD, Faye de Wilt1BSc, Susanne Bogers1MSc, Lennert Gommers1BSc, Daryl Geers1Marianne W. van der Ent10MSc, P. Martin van Hagen10,11MD PhD, Jelle W. van Haga5BSc, Bregtje A. Lemkes5MD PhD, Annelou van der Veen5BSc, Rogier W. Sanders3PhD, Karlijn van der Straten3MD, Judith A. Burger3, BSc, Jacqueline van Rijswijk3BSc, Khadija Tejjani3BSc, Joey H. Bouhuijs3BSc, Karina de Leeuw7MD PhD, Annick A.J.M. van de Ven7MD PhD, S.F.J. de Kruijf-Bazen6MSc, Pieter van Paassen6MD PhD, Lotte Wieten6PhD, Petra H. Verbeek-Menken8BSc, Annelies van Wengen8MSc, Anke H.W. Bruns4MD PhD, Helen L. Leavis4MD PhD, Stefan Nierkens12, 13PhD12Center for Translational Immunology, UMC Utrecht, The Netherlands13Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

Funding Information:
Funded by ZonMw (10430072010006). MJG received funding from the Amsterdam UMC Fellowship to support her research activities.

Publisher Copyright:
© 2023, The Author(s).

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