S05.1 Efficacy and safety of the anti-SARS-CoV-2 BNT162b2 vaccine among SLE patients: the covalus project

Abstract

PurposeVaccination in patients with autoimmune disease like systemic lupus erythematosus (SLE) raises a special concern because its impact on autoimmunity remains partially unknown. While clinical data from large cohort are reassuring [1], very little has been described on the post vaccination immune system reaction. Besides, long-term efficacy of the vaccine, especially regarding T-cell response has not been evaluated in detail.MethodsWe conducted a prospective observational study that included all the adult SLE patients vaccinated by the BNT162b2 anti-SARS-CoV-2 vaccine in a single tertiary medical center in Paris. We evaluated the efficacy and the safety of the vaccine just before the first dose and then one month (M1), three months (M3) and six months (M6) later. Apart from the standard clinical and biological follow-up, we measured, at each time, the proportion of plasmacytoid dendritic cells (PDCs) producing interferon-α (IFN-α) using intracellular flow cytometry staining. We quantified the activation of autoimmune T cells at each visit by stimulating the peripheral blood mononuclear cells (PBMCs) with nuclear antigens and quantifying the proportion of activated (CD154+ CD69+) among non-naïve (CD45-RA -) CD4 T cells. We also evaluated the anti-SARS-CoV-2 T cell response by an Interferon Gamma Release Assay (IGRA) test.ResultsWe included 57 SLE patients and 11 healthy volunteers (HV) vaccinated by the BNT162b2 vaccine according to the French national recommendations. SLE patients were mostly female (49/57, 86.0%) with a median [IQR] age of 44.0 [38.1–50.8] years and a time since SLE diagnosis of 10.8 [4.2–19-8] years. Their treatment regimen was heterogeneous: 47/57 (82.5%) received hydroxychloroquine;35 (61.4%) steroids, and 10 (17.5%) were on another immunosuppressive drug (mycophenolate mofetil, azathioprine or rituximab). We observed only one clinical SLE flare during the post vaccination follow-up. Except for this patient, we observed no modification in the anti-dsDNA titer among SLE patients. At M3 compared to T0, we observed more PDCs producing INF-α in the SLE group: 1.17% [0.72–1.77] vs 0.68% [0.34–1.18], p=0.002 but not in the HV group. The proportion of non-naïve CD4 T cells activated (CD154+ CD69+) by the nuclear antigens did not change after vaccination. Regarding the T cell response, we observed that 71% of the SLE patients had a positive IGRA test at M3, whereas at M6, only 36% of them had a positive IGRA test. The antiviral T cell response correlated well with the humoral response: there was no patient with negative anti-Spike serology and positive IGRA and 78% of patients with a positive serology had a positive IGRA test.ConclusionWe observed that BNT162b2 vaccine had a mild impact on innate and adaptative immunity on SLE patients. The antiviral T cell response was well correlated to the humoral anti-Spike response and decreased significantly from M3 to M6.