Humoral and Cellular Immunogenicity and Safety of Five Different SARS-CoV-2 Vaccines in Patients With Autoimmune Rheumatic and Musculoskeletal Diseases in Remission or With Low Disease Activity and in Healthy Controls: A Single Center Study

Abstract

BackgroundVaccine-induced immunity is essential for controlling the COVID-19 pandemic. Data on humoral and cellular immunogenicity and safety of different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases (RMDs) are limited.MethodsA single center observational study evaluated the immunogenicity and safety of the two-dose regimen of the BBIBP-CorV inactivated, Gam-COVID-Vac and AZD1222 adenovirus-based, and BNT162b2 and mRNA-1273 mRNA-based vaccines in patients with RMDs (n = 89) compared with healthy controls (n = 74). Neutralizing anti-RBD (receptor binding domain) specific antibodies and SARS-CoV-2 specific T-cell response were measured one and four months after the second vaccine dose in parallel with vaccination efficacy and safety.ResultsDisease-specific comparison showed that antibody response at four months was higher in spondylarthropathies compared to rheumatoid arthritis and autoimmune RMDs. Risk factors for reduced immunogenicity included longer disease duration, positive immunoserological profile and anti-CD20 therapy of patients. The rate of positive anti-RBD antibody response for healthy controls versus patients after 4 months post vaccination was 69% vs. 55% for the inactivated viral vaccine BBIBP-CorV, 97% vs. 53% for the pooled data of adenovirus vector-based vaccines Gam-COVID-Vac and AZD1222, or 100% vs. 81% for the pooled data of mRNA vaccines BNT162b2 and mRNA-1273, respectively. Patients who received the Gam-COVID-Vac or mRNA-1273 vaccines had a higher proportion of TNF-α producing CD4+ T-cells upon SARS-CoV-2 antigen stimulation compared to the inactivated viral vaccine.ConclusionAll five investigated vaccines were immunogenic in the majority of patients and healthy controls with variable antibody and T-cell response and an acceptable safety profile.

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

“… Bitoun S. 2021 [ 15 ], France 59 RA; SLE; SSc; Vasculites RTX (24 pts) DMARDs, bDMARDs, MMF, bendamustine, CSs (35 pts) RTX: 29.2% Other immune-suppressors: 80% CD4 and CD8 cellular responses similar between the two groups and to HCs Farroni C. 2022 [ 22 ], Italy 35 RA TNF -α inhibitors, DMARD, IL-6 inhibitors, CSs, ABA 91.4% 65.7% Prendecki M. 2021 [ 16 ], UK 42 SLE; AAV nd SLE 7/8 (87.5%) AAV 17/34 (50%) SLE 2/2 (100%) AAV 15/19 (78.9%) Szebeni G.J. 2022 [ 23 ], Hungary 89 RA; SLE; SSc; AAV; SSj LVV; Spa; PsA CSs, bDMARDs, cDMARDs, Belimumab Vaccine-based stratification: 55% for BBIBP-CorV vaccine, 53% for Gam-COVIDVac and AZD1222 vaccine, 81% for BNT162b2 and mRNA-1273 vaccine Vaccine-based stratification: 20% for BBIBP-CorV vaccine, 32% for Gam-COVID-Vac and AZD1222 vaccine 32% for BNT162b2 and mRNA-1273 vaccine Oyaert M. et al 2022 [ 17 ], Belgium 21 RA, SSc, SLE, PsA, AAV, polymyositis, IgA granulomatosis RTX, DMARD, CSs, MTX, belimumab, adalimumab, 11/21 (52.4%) 9/21 (42.9%) Sieiro Santos C. et al. 2022 [ 24 ], Spain I cohort (ongoing immune-suppressors):100 II cohort (no immune-suppressors): 47 …”

“…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] ].…”

“…The majority of the available studies assessed the T cell response among ASD patients after the first 1–2 doses of COVID-19 vaccination [ [15] , [16] , [17] , 19 , [22] , [23] , [24] ] but results concerning both humoral and cellular post booster immunogenicity are still very limited [ 14 , 18 , 25 , 26 ].…”

Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients

“…Furthermore, two doses of vaccines lead to significantly better outcomes of breakthrough COVID-19 compared with unvaccinated patients [ 11 ]. Data also supported that underlying aiRMDs even in patients in remission or with associated use of immune modifying drugs could attenuate responses to SARS-CoV-2 vaccination [ 12 , 13 ].…”

“…In spring 2021, we had the opportunity to vaccinate our RMD patient’s frontline with two doses of one type of COVID-19 vaccine in our center selected from 5 available vaccines (BBIBP-CorV; Gam-COVID-Vac; AZD1222; BNT162b2; mRNA-1273) [ 12 ]. In autumn 2021, patients received booster vaccination with BNT162b2 vaccine 6 months after the second dose or underwent SARS-CoV-2 infection as a third exposure to SARS-CoV-2 antigens, with significantly different immunogenicity reported in our current study.…”