Article Text
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.
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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.
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.
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