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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Primary Immunodeficiencies
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1501908

Humoral and cell-mediated immune responses to COVID-19 vaccines up to 6 months post 3dose primary series in adults with inborn errors of immunity and their breakthrough infections

Provisionally accepted
Dana Unninayar Dana Unninayar 1Emilia Liana Falcone Emilia Liana Falcone 2Hugo Chapdelaine Hugo Chapdelaine 2Donald C. Vinh Donald C. Vinh 3Karina A. Top Karina A. Top 4Beata Derfalvi Beata Derfalvi 5THOMAS B ISSEKUTZ THOMAS B ISSEKUTZ 5Hélène Decaluwe Hélène Decaluwe 6Anne Pham-Huy Anne Pham-Huy 7Julia Upton Julia Upton 8Stephen Betschel Stephen Betschel 9Tamar Rubin Tamar Rubin 10Sneha Suresh Sneha Suresh 11Nicola Wright Nicola Wright 12Luis Enrique Murguia-Favela Luis Enrique Murguia-Favela 12Tatiana Kalashnikova Tatiana Kalashnikova 12Lisa Barrett Lisa Barrett 13Sharon Oldford Sharon Oldford 13Marc-André Langlois Marc-André Langlois 14Corey Arnold Corey Arnold 14Manish Sadarangani Manish Sadarangani 15Tinghua Zhang Tinghua Zhang 1Tim Ramsay Tim Ramsay 1Dina Yazji Dina Yazji 14Juthaporn Cowan Juthaporn Cowan 1,14*
  • 1 Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada
  • 2 Montreal Clinical Research Institute (IRCM), Montréal, Quebec, Canada
  • 3 McGill University Health Centre, Montreal, Quebec, Canada
  • 4 Pediatrics, Dalhouse University, IWK Health, Halifax, Nova Scotia, Canada
  • 5 Pediatrics, Dalhousie University, IWK Health, Halifax, Nova Scotia, Canada
  • 6 Centre de Recherche, CHU Sainte-Justine, Montreal, Quebec, Canada
  • 7 Children's Hospital of Eastern Ontario (CHEO), Ottawa, Ontario, Canada
  • 8 Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 9 Clinical Immunology and Allergy, Unity Health Toronto, Toronto, Ontario, Canada
  • 10 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
  • 11 Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  • 12 Alberta Children's Hospital, Calgary, Alberta, Canada
  • 13 Department of Medicine, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  • 14 Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
  • 15 Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

The final, formatted version of the article will be published soon.

    Many individuals with inborn errors of immunity (IEI) have poor humoral immune (HI) vaccine responses. Only few studies have examined specific cell-mediated immune (CMI) responses to Coronavirus disease-19 vaccines in this population. Therefore, the purpose of this study is to examine HI and CMI responses up to 6-months post-COVID-19 vaccine dose 3 in adults with IEI.A multi-center prospective observational study was conducted across Canada to collect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) specific HI and CMI data at 4 and 24week intervals after vaccine doses 2 and 3 (D2+4wk/D2+24wk/D3+4wk/D3+24wk).149 adults with IEI and 423 healthy controls were recruited from July 2021 to October 2023. Geometric mean anti-spike IgG (Binding Antibody Unit/mL) and spike-specific T-cell responses (IFN-γ + T-cells/10 6 PBMC) were significantly lower in IEI compared to controls at D2+4wk, D3+4wk, and D3+24wk. However, at 6-months after completing primary series (3 doses for IEI and 2 doses for healthy), both HI and CMI responses of both IEI and healthy controls persisted and were comparable. There was a strong correlation between neutralizing antibody titer (ID50) and anti-spike IgG but not between ID50 and CMI. There was only one reported case of hospitalized COVID-19 disease before and none after completing primary series among IEI participants.Adults with IEI mounted both HI and CMI responses following COVID-19 vaccines that were lower than healthy individuals but were present at least up to 6-months after dose 3. This data supports the initial recommendation for a three-dose primary series among IEI.

    Keywords: COVID-19, vaccine response, Inborn error of immunity, humoral immunity, cellular mediated immunity, Immunogenicity

    Received: 25 Sep 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Unninayar, Falcone, Chapdelaine, Vinh, Top, Derfalvi, ISSEKUTZ, Decaluwe, Pham-Huy, Upton, Betschel, Rubin, Suresh, Wright, Murguia-Favela, Kalashnikova, Barrett, Oldford, Langlois, Arnold, Sadarangani, Zhang, Ramsay, Yazji and Cowan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Juthaporn Cowan, Ottawa Hospital Research Institute (OHRI), Ottawa, K1Y 4E9, Ontario, Canada

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.