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Nat Med ; 27(11): 1990-2001, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34522051

RESUMEN

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.


Asunto(s)
Vacunas contra la COVID-19/uso terapéutico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/terapia , SARS-CoV-2/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/sangre , Antígenos CD20/inmunología , COVID-19/prevención & control , Estudios de Casos y Controles , Chlorocebus aethiops , Células HEK293 , Humanos , Inmunidad Celular , Inmunidad Humoral/efectos de los fármacos , Inmunidad Humoral/fisiología , Inmunoterapia/métodos , Estudios Longitudinales , Esclerosis Múltiple/sangre , ARN Mensajero/inmunología , ARN Viral/inmunología , Rituximab/farmacología , Rituximab/uso terapéutico , SARS-CoV-2/genética , Vacunación , Células Vero
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