Antigen Specific Humoral and Cellular Immunity Following SARS-CoV-2 Vaccination in ANCA-Associated Vasculitis Patients Receiving B-Cell Depleting Therapy

Abstract

Humoral vaccine responses are known to be suboptimal in patients receiving B-cell targeted therapy, and little is known about vaccine induced T-cell immunity in these patients. In this study, we characterized humoral and cellular antigen-specific anti-SARS-CoV2 responses following COVID-19 vaccination in patients with ANCA-associated vasculitis (AAV) receiving anti-CD20 therapy, who were either B-cell depleted, or B-cell recovered at the time of vaccination and in normal control subjects. SARS-CoV-2 anti-spike (S) and anti-nucleocapsid (NC) antibodies were measured using electrochemiluminescence immunoassays, while SARS-CoV-2 specific T-cell responses to S glycoprotein subunits 1 (S1) and 2 (S2) and receptor binding domain peptide pools were measured using interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. In total, 26 recently vaccinated subjects were studied. Despite the lack of a measurable humoral immune response, B-cell depleted patients mounted a similar vaccine induced antigen-specific T-cell response compared to B-cell recovered patients and normal controls. Our data indicate that to assure a humoral response in patients receiving anti-CD20 therapy, SARS-CoV-2 vaccination should ideally be delayed until B-cell recovery (CD-20 positive B-cells > 10/μl). Nevertheless, SARS-CoV-2 vaccination elicits robust, potentially protective cellular immune responses in these subjects. Further research to characterize the durability and protective effect of vaccine-induced anti-SARS-CoV-2 specific T-cell immunity are needed.

COVID-19 vaccine immunogenicity in 16 patients with autoimmune systemic diseases. Lack of both humoral and cellular response to booster dose and ongoing disease modifying therapies

“… 2022 [ 24 ], Spain I cohort (ongoing immune-suppressors):100 II cohort (no immune-suppressors): 47 RA, SLE, SS, pSS I cohort: MTX, AZA, MMF, LFM and/or bDMARDs (Belimumab, ABA, RTX) II cohort: Non-steroidal anti-inflammatory drugs and/or infliximab, tocilizumab, anakinra I cohort Seroconversion: 55% II cohort Seroconversion: 80% Th1 response 52% CD8 response 77% Th1 response 75% CD8 response 53% Marty P·K. 2022 [ 21 ], USA 17 AAV 11 B-cell depleted 8 B-cell recovered 0% 100% 90.9% 88.9% After the booster dose of COVID-19 vaccine Corradini P. et al 2022 [ 26 ], Italy 37 AAV, SSc, mixed connective tissue disease, SLE, pSS, DM, polymyositis, and RA MTX, MMF, AZA, cyclosporine, RTX, CSs 90% 89.2% Firinu D. et al 2022 [ 18 ], Italy 31 RA, SLE, Connective Tissue Disease; MS RTX; OCRE; ADA; ETN; MTX; MMF; csDMARDs 55% among the RTX group, 100% in IMID (immune-mediated inflammatory diseases, naïve to RTX) 21 (68%) 79% among the RTX group, 50% in IMID Azzolini E. et al 2022 [ 25 ], Italy 30 PA/SpA/AS, RA, SLE, DM, pSS, SSc MTX, MMF 96.6% 80% Ag1 83.3% Ag2 Jyssum I. et al …”

“…Nevertheless, there is still controversy regarding the T cell response in the ASD setting due to the variability of the diagnoses and to the different effect of ongoing disease modifying therapies (DMT) on the cellular immunity [ [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] ].…”

Immunity to SARS-CoV-2: What Do We Know and Should We Be Testing for It?

“…Importantly however, they note that only 48% of participants achieved antibody levels exceeding 4,160 AU/mL, which is considered a surrogate measure of vaccine protection according to the anti-spike assay manufacturer (Abbott Architect SARS-CoV-2 IgG Quant II, Abbott, Sligo, Ireland). Finally, it is important to note that despite limited antibody responses following vaccination of immunosuppressed patients, particularly those who are B-cell deficient, the majority of patients remain capable of developing strong cellular, T-cell mediated immune responses as measured by IFN-γ presence following stimulation with different spike antigen epitopes ( 48 – 50 ).…”

Glucocorticoid use as a cause of non-cellular immune response to SARS-Cov2 Spike in patients with immune system diseases

“…Indeed, it has been established that glucocorticoids (GC), antimetabolite therapies such as methotrexate (MTX) or mycophenolate mofetil (MMF), and anti-CD20 B cell targeted monoclonal antibody (mAb) increase the risk of hospitalization, and severe/fatal outcomes resulting from SARS-Cov2 infections [ 1 , 2 ]. It has further been shown that there is an association between DMT exposure and a lower humoral response after COVID-19 vaccination in ISD patients [ 3 ], which led to the proposal to stop MTX or delaying anti-CD20 mAb therapy to increase patients' chances of responding well to the vaccine [ 4 , 5 ]. Furthermore, the French health authorities recommend anti-SARS-Cov2 prophylactic therapies to vaccinated ISD patients when the titer of anti-Spike antibodies is above 264 binding antibody units (BAU).…”