Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

• Published in: Annals of the rheumatic diseases Vol. 81; no. 5; pp. 720 - 728
• Main Authors: Hadjadj, Jerome, Planas, Delphine, Ouedrani, Amani, Buffier, Solene, Delage, Laure, Nguyen, Yann, Bruel, Timothée, Stolzenberg, Marie-Claude, Staropoli, Isabelle, Ermak, Natalia, Macraigne, Laure, Morbieu, Caroline, Henriquez, Soledad, Veyer, David, Péré, Hélène, Casadevall, Marion, Mouthon, Luc, Rieux-Laucat, Frederic, Chatenoud, Lucienne, Schwartz, Olivier, Terrier, Benjamin
• Format: Journal Article
• Language: English
• Published: United States BMJ Publishing Group Ltd and European League Against Rheumatism 01.05.2022; Elsevier Limited; BMJ Publishing Group
• Subjects: Antibodies; Antibodies, Viral; BNT162 Vaccine; Coronaviruses; Covid-19; COVID-19 - prevention & control; COVID-19 Vaccines; Drug dosages; Epidemiology; Flow cytometry; Humans; Immune response (humoral); Immunization; Immunocompromised Host; Immunocompromised hosts; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G; Immunosuppressive agents; Immunotherapy; Inflammatory diseases; Influenza; Life Sciences; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical personnel; Methotrexate; Monoclonal antibodies; Patients; Peptides; Prospective Studies; Rituximab; SARS-CoV-2; Seroconversion; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; vaccination; Vaccines; India; methotrexate; Covid-19; rituximab; vaccination
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2021-221508

ObjectivesThe 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.MethodsProspective 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.ResultsSixty-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.ConclusionRituximab 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).