You are here

  • Home
  • Archive
  • Volume 81, Issue 5
  • Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

Article Text

Article menu
Download PDFPDF
Epidemiology
Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases
  1. Jerome Hadjadj1,
  2. Delphine Planas2,3,
  3. Amani Ouedrani4,
  4. Solene Buffier1,
  5. Laure Delage5,6,
  6. Yann Nguyen7,8,
  7. Timothée Bruel2,3,
  8. Marie-Claude Stolzenberg5,
  9. Isabelle Staropoli3,
  10. Natalia Ermak9,
  11. Laure Macraigne4,
  12. Caroline Morbieu1,
  13. Soledad Henriquez1,
  14. David Veyer10,11,
  15. Hélène Péré10,11,
  16. Marion Casadevall1,
  17. Luc Mouthon1,
  18. Frederic Rieux-Laucat5,
  19. Lucienne Chatenoud4,
  20. Olivier Schwartz2,3,
  21. Benjamin Terrier1
  1. 1 Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP.CUP, Hôpital Cochin, Paris, France
  2. 2 Vaccine Research Institute, Creteil, France
  3. 3 Virus & Immunity Unit, Department of Virology, Institut Pasteur; CNRS UMR 3569, Paris, France
  4. 4 Laboratoire d’Immunologie Biologique, Université de Paris, Paris, Institut Necker-Enfants Malades-CNRS UMR8253, Inserm UMR1151, AP-HP, APHP.CUP, Hôpital Necker-Enfants Malades, Paris, France
  5. 5 Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Université de Paris, Institut Imagine, INSERM UMR 1163, F-75015, Paris, France
  6. 6 Checkpoint Immunology, Immunology and Inflammation Therapeutic Area, Sanofi, Vitry-sur-Seine, France
  7. 7 Health across Generations Team, Center for Research in Epidemiology and Population Health, (CESP), Institut pour la Santé et la Recherche Médicale (INSERM) U1018, Université Paris-Saclay, Université Paris-Sud, Villejuif, France
  8. 8 Department of Internal Medicine, APHP.Nord, Hôpital Beaujon, Université de Paris, Clichy, France
  9. 9 Department of General Biochemistry, Hôpital Cochin, Paris, France
  10. 10 Functional Genomics of Solid Tumors (FunGeST), INSERM, Centre de Recherche des Cordeliers, Université de Paris and Sorbonne Université, Paris, France
  11. 11 Laboratoire de Virologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, Paris, France
  1. Correspondence to Prof. Benjamin Terrier, Department of Internal Medicine, Hôpital Cochin, Paris, France; benjamin.terrier{at}aphp.fr

Abstract

Objectives The emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. We aimed to evaluate seroconversion, cross-neutralisation and T-cell responses induced by BNT162b2 in immunocompromised patients with systemic inflammatory diseases.

Methods Prospective monocentric study including patients with systemic inflammatory diseases and healthcare immunocompetent workers as controls. Primary endpoints were anti-spike antibodies levels and cross-neutralisation of Alpha and Delta variants after BNT162b2 vaccine. Secondary endpoints were T-cell responses, breakthrough infections and safety.

Results Sixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analysed. Kinetics of anti-spike IgG after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralising response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralised Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralising activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after two doses of BNT162b2. Third dose of vaccine improved immunogenicity in patients with low responses.

Conclusion Rituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (ClinicalTrials.gov number, NCT04870411).

  • vaccination
  • rituximab
  • methotrexate
  • Covid-19

Data availability statement

Data are available upon reasonable request. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/annrheumdis-2021-221508

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data are available upon reasonable request. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

    View Full Text

    Footnotes

    • FR-L, LC and OS are joint senior authors.

    • Handling editor Josef S Smolen

    • Twitter @HadjadjJerome, @TerrierBen

    • JH, DP and AO contributed equally.

    • SB, LD and YN contributed equally.

    • Collaborators Philippe Blanche, Benjamin Chaigne, Pascal Cohen, Nathalie Costedoat-Chalumeau, Bertrand Dunogué, Laure Frumholtz, Gaelle Guettrot-Imbert, Véronique Le Guern, Loic Guillevin, Claire Le Jeunne, Xavier Puechal, Tali-Anne Szwebel

    • Contributors All authors contributed to manuscript preparation. BT is responsible for the overall content as the guarantor. JH and BT contributed to the study design. DP, IS and TB performed antibody measurement, neutralisation assay and data analysis. AO and LC contributed to cellular assays, data analysis and manuscript preparation. JH, BT, DP, TB, LD, YN, SB, OS and LC performed data analysis. LD and MCS performed lymphocytes phenotyping.

    • Funding This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology. Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash COVID-19 PROTEO-SARS-CoV-2 and IDISCOVR. DP is supported by the Vaccine Research Institute

    • Competing interests TB, IS and OS are coinventors on provisional patent no. US 63/020,063 entitled ‘S-Flow: a FACS-based assay for serological analysis of SARS-CoV-2 infection’ submitted by Institut Pasteur.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.