PT  - JOURNAL ARTICLE
AU  - Jerome Hadjadj
AU  - Delphine Planas
AU  - Amani Ouedrani
AU  - Solene Buffier
AU  - Laure Delage
AU  - Yann Nguyen
AU  - Timothée Bruel
AU  - Marie-Claude Stolzenberg
AU  - Isabelle Staropoli
AU  - Natalia Ermak
AU  - Laure Macraigne
AU  - Caroline Morbieu
AU  - Soledad Henriquez
AU  - David Veyer
AU  - Hélène Péré
AU  - Marion Casadevall
AU  - Luc Mouthon
AU  - Frederic Rieux-Laucat
AU  - Lucienne Chatenoud
AU  - Olivier Schwartz
AU  - Benjamin Terrier
TI  - Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases
AID  - 10.1136/annrheumdis-2021-221508
DP  - 2022 Jan 11
TA  - Annals of the Rheumatic Diseases
PG  - annrheumdis-2021-221508
4099  - http://ard.bmj.com/content/early/2022/01/11/annrheumdis-2021-221508.short
4100  - http://ard.bmj.com/content/early/2022/01/11/annrheumdis-2021-221508.full
AB  - 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).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.