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 Paassen; Karina 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

doi:10.1016/j.jaci.2022.04.002

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 journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	1949-1957
Number of pages	9
Journal	Journal of Allergy and Clinical Immunology
Volume	149
Issue number	6
DOIs	https://doi.org/10.1016/j.jaci.2022.04.002
Publication status	Published - Jun 2022

Keywords

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

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van Leeuwen, L. P. M., GeurtsvanKessel, C. H., Ellerbroek, P. M., de Bree, G. J., Potjewijd, J., Rutgers, A., Jolink, H., van de Veerdonk, F., van Gorp, E. C. M., de Wilt, F., Bogers, S., Gommers, L., Geers, D., Bruns, A. H. W., Leavis, H. L., van Haga, J. W., Lemkes, B. A., van der Veen, A., de Kruijf-Bazen, S. F. J., ... Dalm, V. A. S. H. (2022). Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity. Journal of Allergy and Clinical Immunology, 149(6), 1949-1957. https://doi.org/10.1016/j.jaci.2022.04.002

@article{14991e5ab9c740b1b4cca6904fa5ec08,

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

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.",

keywords = "antibody response, CID, CVID, immunogenicity, Inborn errors of immunity, mRNA-1273 COVID-19 vaccine, primary immunodeficiency disorders, SARS-CoV-2, T-cell response, XLA",

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

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: {\textcopyright} 2022 The Authors",

year = "2022",

month = jun,

doi = "10.1016/j.jaci.2022.04.002",

language = "English",

volume = "149",

pages = "1949--1957",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "6",

}

van Leeuwen, LPM, GeurtsvanKessel, CH, Ellerbroek, PM, de Bree, GJ, Potjewijd, J, Rutgers, A, Jolink, H, van de Veerdonk, F, van Gorp, ECM, de Wilt, F, Bogers, S, Gommers, L, Geers, D, Bruns, AHW, Leavis, HL, van Haga, JW, Lemkes, BA, van der Veen, A, de Kruijf-Bazen, SFJ, van Paassen, P, de Leeuw, K, van de Ven, AAJM, Verbeek-Menken, PH, van Wengen, A, Arend, SM, Ruten-Budde, AJ, van der Ent, MW, van Hagen, PM, Sanders, RW, Grobben, M, van der Straten, K, Burger, JA, Poniman, M, Nierkens, S, van Gils, MJ, de Vries, RD & Dalm, VASH 2022, 'Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity', Journal of Allergy and Clinical Immunology, vol. 149, no. 6, pp. 1949-1957. https://doi.org/10.1016/j.jaci.2022.04.002

TY - JOUR

T1 - Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity

AU - van Leeuwen, Leanne P.M.

AU - GeurtsvanKessel, Corine H.

AU - Ellerbroek, Pauline M.

AU - de Bree, Godelieve J.

AU - Potjewijd, Judith

AU - Rutgers, Abraham

AU - Jolink, Hetty

AU - van de Veerdonk, Frank

AU - van Gorp, Eric C.M.

AU - de Wilt, Faye

AU - Bogers, Susanne

AU - Gommers, Lennert

AU - Geers, Daryl

AU - Bruns, Anke H.W.

AU - Leavis, Helen L.

AU - van Haga, Jelle W.

AU - Lemkes, Bregtje A.

AU - van der Veen, Annelou

AU - de Kruijf-Bazen, S. F.J.

AU - van Paassen, Pieter

AU - de Leeuw, Karina

AU - van de Ven, Annick A.J.M.

AU - Verbeek-Menken, Petra H.

AU - van Wengen, Annelies

AU - Arend, Sandra M.

AU - Ruten-Budde, Anja J.

AU - van der Ent, Marianne W.

AU - van Hagen, P. Martin

AU - Sanders, Rogier W.

AU - Grobben, Marloes

AU - van der Straten, Karlijn

AU - Burger, Judith A.

AU - Poniman, Meliawati

AU - Nierkens, Stefan

AU - van Gils, Marit J.

AU - de Vries, Rory D.

AU - Dalm, Virgil A.S.H.

N1 - 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

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - antibody response

KW - CID

KW - CVID

KW - immunogenicity

KW - Inborn errors of immunity

KW - mRNA-1273 COVID-19 vaccine

KW - primary immunodeficiency disorders

KW - SARS-CoV-2

KW - T-cell response

KW - XLA

UR - http://www.scopus.com/inward/record.url?scp=85128647679&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2022.04.002

DO - 10.1016/j.jaci.2022.04.002

M3 - Article

C2 - 35421449

AN - SCOPUS:85128647679

SN - 0091-6749

VL - 149

SP - 1949

EP - 1957

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 6

ER -

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

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