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 ).
Keywords: Covid-19; methotrexate; rituximab; vaccination.
【저자키워드】 COVID-19, rituximab, vaccination., methotrexate, 【초록키워드】 Inflammatory diseases, SARS-CoV-2, Vaccine, BNT162b2 vaccine, vaccination, immunogenicity, T-cell Response, Immunocompromised patients, Delta, B.1.617.2, delta variant, rituximab, Immunocompromised patient, BNT162b2, Kinetics, Seroconversion, Viral, Humoral response, Immune escape, anti-Spike IgG, sera, healthcare, Prospective, therapeutic, Patient, Control, Alpha, breakthrough infections, Breakthrough infection, T-cell, methotrexate, Other, Strains, anti-spike antibodies, neutralisation, T-cell responses, anti-spike antibody, Delta variants, Neutralising activity, B-cell, dose, strain, humoral, regimen, Support, Endpoint, immunocompromised individuals, primary endpoints, Secondary endpoints, individual, effort, Specific T-cell response, alpha and delta variants, viral fitness, responses, controls, secondary, neutralising, systemic inflammatory diseases, raise, IMPROVE, evaluate, analysed, treated, abrogated, exhibiting, immunocompromised individual, impairing, infected with SARS-CoV-2, mounted, of BNT162b2, systemic inflammatory disease, 【제목키워드】 Vaccine, Immunocompromised patient, of BNT162b2, systemic inflammatory disease,