Cellular and humoral responses after second and third SARS-CoV-2 vaccinations in patients with autoimmune diseases treated with rituximab: specific T cell immunity remains longer and plays a protective role against SARS-CoV-2 reinfections

Natalia Egri; Hugo Calderón; Robert Martinez; Mario Vazquez; Verónica Gómez-Caverzaschi; Mariona Pascal; Olga Araújo; Manel Juan; Europa Azucena González-Navarro; José Hernández-Rodríguez

doi:10.3389/fimmu.2023.1146841

Cellular and humoral responses after second and third SARS-CoV-2 vaccinations in patients with autoimmune diseases treated with rituximab: specific T cell immunity remains longer and plays a protective role against SARS-CoV-2 reinfections

Front Immunol. 2023 Apr 27:14:1146841. doi: 10.3389/fimmu.2023.1146841. eCollection 2023.

Affiliations

¹ Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Center of the European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) and ERN on Connective Tissue and Musculoskeletal Diseases (ReCONNET); Spanish Center of the Centros, Servicios y Unidades de Referencia (CSUR) and Catalan Center of the Xarxa d'Unitats d'Expertesa Clínica (XUEC) for Autoinflammatory Diseases, Autoimmune Diseases and Primary Immunodeficiencies, Barcelona, Spain.
² Clinical Unit of Autoinflammatory Diseases and Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Center of the European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) and ERN on Connective Tissue and Musculoskeletal Diseases (ReCONNET), Spanish Center of the Centros, Servicios y Unidades de Referencia (CSUR) and Catalan Center of the Xarxa d'Unitats d'Expertesa Clínica (XUEC) for Autoinflammatory Diseases, Autoimmune Diseases and Primary Immunodeficiencies, Barcelona, Spain.

Abstract

Background: Humoral and cellular immune responses are known to be crucial for patients to recover from COVID-19 and to protect them against SARS-CoV-2 reinfection once infected or vaccinated.

Objectives: This study aimed to investigate humoral and T cell responses to SARS-CoV-2 vaccination in patients with autoimmune diseases after the second and third vaccine doses while on rituximab and their potential protective role against reinfection.

Methods: Ten COVID-19-naïve patients were included. Three time points were used for monitoring cellular and humoral responses: pre-vaccine to exclude virus exposure (time point 1) and post-second and post-third vaccine (time points 2 and 3). Specific IgG antibodies were monitored by Luminex and T cells against SARS-CoV-2 spike-protein by ELISpot and CoVITEST. All episodes of symptomatic COVID-19 were recorded.

Results: Nine patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and one with an undifferentiated autoimmune disease were included. Nine patients received mRNA vaccines. The last rituximab infusion was administered for a mean (SD) of 15 (10) weeks before the first vaccine and six patients were CD19-B cell-depleted. After a mean (SD) of 19 (10) and 16 (2) days from the second and third vaccine dose, IgG anti-SARS-CoV-2 antibodies were detected in six (60%) and eight (80%) patients, respectively. All patients developed specific T cell responses by ELISpot and CoVITEST in time points 2 and 3. Previous B cell depletion correlated with anti-SARS-CoV-2 IgG levels. Nine (90%) patients developed mild COVID-19 after a median of 7 months of the third dose.

Conclusion: Rituximab in patients with autoimmune diseases reduces humoral responses but does not avoid the development of T cell responses to SARS-CoV-2 vaccination, which remain present after a booster dose. A steady cellular immunity appears to be protective against subsequent reinfections.

Keywords: COVID - 19; SARS-CoV-2 vaccines; anti CD-20; autoimmune diseases; cellular response; humoral response; rituximab; vasculitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis*
Antibodies, Viral
Autoimmune Diseases* / drug therapy
COVID-19 Vaccines
COVID-19*
Humans
Immunoglobulin G
Reinfection
Rituximab / therapeutic use
SARS-CoV-2
T-Lymphocytes
Vaccination

Substances

COVID-19 Vaccines
Rituximab
Immunoglobulin G
Antibodies, Viral

Grants and funding

This study received funding from ”La Caixa” Foundation under the grant agreement LCF/PR/HR22/52420015 and from CELLNEX TELECOM (5234-20/CPO42837) through ACT4COVID consortium. NE is a recipient of the grant “Contracte Clıínic de Recerca Emili Letang–Josep Font”. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.