146. The Effect of Immunosuppressive Therapy on Adaptive Immune Responses to COVID-19 Vaccination in AAV Patients
Creators: name: Leacy1, Emma
name: Jean Dunne1, 2
name: Niall Conlon1, 2
name: Matthew Griffin3, 4
name: Ibrahim1, Aya
name: Brady1, Gareth
name: McCormack1, William
name: Zgaga1, Lina
name: O'Shaughnessy5, Michelle
name: Mark Little1, 6
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> As the COVID-19 pandemic proceeds, it is vital to understand how immunosuppressive therapies impact vaccine immunogenicity, so that vaccine strategies encompassing timing, nature, and frequency of treatment, can be tailored to optimise efficacy in immunosuppressed patients. We profiled serological and whole blood immune cell responses to SARS-CoV-2 vaccination, according to immunosuppression exposure status in a national population of adults with ANCA vasculitis (AAV). <strong>Methods:</strong> Patients were sampled before and after completion of a COVID-19 vaccine course, and again 4-6 weeks following their 3<sup>rd</sup> vaccine dose. Immunosuppression exposure was categorised as: i) No immunosuppressive therapy (including &lt;10mg prednisolone currently); ii) Rituximab exposure (within previous 6 months, or at any time with persistent B-cell depletion); iii) Other immunosuppression (current prednisolone ≥10mg, cyclophosphamide within previous 6 months, or current use of another immunosuppressive agent). We measured IgG, IgM, IgA and antibodies capable of blocking Spike-ACE2 interaction against SARS-CoV2 Spike protein. A novel interferon gamma response assay (IGRA) was used to assess cellular interferon-γ release, using whole Spike protein, M&amp;N protein and PepTivator SARS-CoV-2 peptides. Deep phenotyping of T cell responses was performed in selected cases. <strong>Results:</strong> Results following the 2<sup>nd</sup> vaccine dose are presented here. Among the 50 patients studied, one was excluded because of serological/IGRA evidence of pre-vaccine SARS-Cov2 exposure. Median age was 65 (IQR 54-73) years, 28 (56%) were male, and 24 (48%) were immunosuppressed: 10 (20%) with Rituximab and 14 (28%) with “other” immunosuppression. 24 (49%) received the AZD1222/ChAdOx1 and 25 (51%) the BNT162b2 mRNA vaccine. Median time to post-vaccine blood sampling was 42 (IQR 35-57) days. T cell responses to SARS-CoV-2 were evident after 2<sup>nd</sup> dose vaccination in 89% of immunosuppressed patients: 57% of “other immunosuppression” exposed, and 83% of non-exposed patients had detectable cellular responses to SARS-CoV-2 (Fig 1A). In contrast, the serological response was impaired in patients exposed to Rituximab (0% had detectable IgG) compared to 77% with other immunosuppression (Fig 1B). Post-vaccine immune responses are summarised in Fig 1C. <strong>Conclusions:</strong> In this national study of patients with AAV, exposure to immunosuppressive therapy – most notably Rituximab – significantly impaired serological response to COVID19 vaccine but had less impact on cellular responses in line with previous observations for other immunosuppressed cohorts. The clinical implications of these findings, immunosuppression choice, timing and frequency of vaccination, and clinical effectiveness of a predominant T-cell response invite further study. <strong>Disclosures:</strong> None <strong>Figure 1.</strong> Cellular (A) and serological (B) responses to SARS-CoV2 vaccination, and paired subject level binary results (C).