157. Immunogenicity of SARS-CoV-2 vaccination in patients receiving immunosuppression

Background: Patients receiving immunosuppression treatment are clinically vulnerable to coronavirus disease 2019 (COVID-19). Phase 3 trials of several vaccine candidates have shown proven immunological and clinical efficacy in the general population but excluded patients receiving immunosuppression or with renal impairment. In this study we describe immunological responses to vaccination with BNT162b2 mRNA or ChAdOx1 nCoV-19 replication-deficient adenoviral vector vaccines in patients with autoimmune glomerular and rheumatic diseases.

Methods: Immunological responses to vaccination were analysed in immunosuppressed patients (IS) and healthy volunteers (HV). In 443 patients, analysis of humoral responses were assessed at any time-point ≥21 days following two-dose vaccination. In a sub-group of 140 patients, and 70 HV analysis of both humoral and cellular responses were assessed at baseline, day 21 after first-dose, day and 6 months after second-dose. Serum was tested for antibodies to nucleocapsid protein using the Abbott Architect SARS-CoV-2 IgG chemiluminescent immunoassay (CMIA) and to spike protein using the quantitative Abbott Architect SARS-CoV-2 IgG Quant II CMIA. SARS-CoV-2 specific T-cell responses were detected using the T-SPOT® Discovery SARS-CoV-2 (Oxford Immunotec).

Results: 443 patients underwent assessment of humoral responses at a median of 31 days after second-dose vaccination. 62.5% received BNT162b2 (n=277) and 37.5% received ChAdOx1 (n=177), median vaccine interval was 65 days (IQR 35-76). Humoral response to vaccination was significantly lower than in those without prior natural infection (median anti-S 130.8 and 3171 BAU/ml respectively, p<0.0001). In infection-naïve patients multivariable analysis identified increasing age (OR 0.97, p0.01), rituximab treatment within 6 months of vaccination (OR 0.26, p=0.0002), B cell depletion at time of vaccination (OR 0.15, p<0.0001), and lower eGFR (OR 1.01, p=0.06) associated with decreased likelihood of seroconversion. When quantitative serological responses were analysed, time between vaccinations (Figure 1A), vaccine type (Figure 1B), and B cell depletion at time of vaccination (Figure 1C) were associated with decreased serological responses. There was inverse correlation between B cell count and anti-S titre (r=0.23, p=0.0005), and time since last rituximab treatment and anti-S titre (r=0.35, p<0.0001). In the sub-group of patients, following 2-dose vaccination, T cell responses were comparable between HV (n=51) and IS patients (n=43) with 83% of IS patients developing detectable T cell responses (Figure 1D). Magnitude of T cell responses was weaker in patients receiving treatment with tacrolimus (median 43 and 152 SFU/10⁶ PBMC in patients treated with tacrolimus and not respectively, p=0.01). At 5-6 months after second-dose vaccination, anti-S titres were significantly lower in both IS (n=105 infection-naïve; median anti-S 11.2 BAU/m) and HV cohorts (Figure 1E; n=45 infection-naïve; median anti-S 107 BAU/ml). Similar to the earlier time point, T cell responses were comparable between IS (n=27, median 38 SFU/10⁶ PBMC) and HV cohorts (Figure 1F; n=36, median 24 SFU/10⁶ PBMC).

Conclusions: COVID-19 vaccines are immunogenic in the majority of patients with GN but serological responses are blunted, particularly in patients treated with rituximab. Age, eGFR, vaccine type and dosing interval also have an impact on seroconversion rates. T cell responses are comparable to HV and the majority of patients have detectable T cell responses to two-dose vaccination. Both serological and cellular responses have waned by 6 months after two-dose vaccination. Since patients with AAV are frequently of older age, treated with rituximab, and may have impaired GFR they are high risk of impaired vaccine responses and should be prioritized for further protective strategies.

Disclosures: PK and MW have received support to use the T-SPOT® Discovery SARS-CoV-2 by Oxford Immunotec.