149. COVID-IGRA' responses post SARS CoV2 vaccination in patients with primary (PID) and secondary (SID) Immunodeficiency
Creators: name: Niall Conlon1, 2
name: Stuart  Hendricken Phelan1, 2
name: Barron1, Ann
name: Crea1, Patricia Mc
name: Keever1, Aoife Mc
name: Sloan1, Anne
name: Alamin1, Salma
name: Sui1, Jacklyn
name: J. David Edgar1, 2
name: Jean Dunne1, 2
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background</strong><strong>:</strong> Patients with PID and SID are at risk from COVID disease. Patients with objective evidence of immunodeficiency have been advised to shield or cocoon, to reduce infection risk. Vaccination offers a possible pandemic exit strategy from these enforcted limitations for such groups. However, little is known about the effect of SARS-CoV2 vaccination on the immune system of patients with immunodeficiency conditions. We estbalished a robust, scalable ‘COVID-IGRA’; A whole blood assay to measure IFN-g release (IGRA) after stimulation with SARS CoV2 antigens. We aimed to use this to assess post COVID vaccine IFN-g responses in controls including healthy older individuals and in patients in a variety of immunodeficiency states <strong>Methods</strong>: Samples were drawn into ‘Qiagen Monitor TM tubes’ and after overnight incubation with SARS CoV2 membrane/ nucleopcapsid peptide mix, spike peptide mix (Miltenyi) or recombinant spike trimer protein, the supernatants were tested by ELISA for IFNγ level. Normal ranges were established using healthy controls pre-vaccination (n=32) and 28-40 days post vaccination (n=40). Patients with PID were invited to participate including Common Variable Immunodeficiency (CVID) (n=27), X-linked Agammaglobulinaemia (XLA) (n=8), other Inborn Errors of Immunity (IEI) (n=8). A comparator group of patients with symptomatic SID were recruited (n=13). This included 9 patients with rituximab treated ANCA vasculitis <strong>Results:</strong> Healthy control assay validation data demonstrated that the SARS CoV2 spike peptide antigen was able to discriminate accurately between pre and post vaccine samples (ROC AUC 0.99). Stimulation with whole spike protein was a less perfect recall antigen in the post vaccine state. 23/27 (85%) of patients with Common Variable Immunodeficiency (CVID) produced a post vaccine IFNg response in whole blood that was comparable to the reference range derived from healthy controls (Figure 1). 8/8 (100%) of XLA patients and 7/8 (87.5%) of other IEI patients produced a similar response. 9/13 (69%) patients with symptomatic SID produced a robust response. Patients with CVID who did not respond had a significantly higher disease severity score (42.75 v 13.8, p&lt;0.01) than those who did respond. Membrane/Nucleocapsid antigen induced IFNg release was suggestive of prior natural infection. <strong>Conclusions:</strong> We established and validated a COVID IGRA. Our assay is scalable, robust, reproducible and suitable for use in a routine diagnostic laboratory. Many patients with objective evidence of PID and SID immunodeficiency produce IFNg responses to SARS CoV2 antigens. However, a higher proportion of patients with SID, including patients on maintenance rituximab, failed to produce a normal IFNg response. Although numbers are small our data suggests that examination of this cohort is desirable. It is currently unknown whether cellular immune responses such as IFNg release in response to recall antigens in the post vaccine state represent correlates of clinical protection. The high proportion of vaccinated PID and SID patients inducing IFNg production, comparable to healthy controls in conditions where humoral immunity is known to be compromised does indicate vaccines are inducing measurable cellular recall responses. This information may be useful in explaining the rationale for vaccination in immunocompromised cohorts. We propose further work correlating our assay with other COVID-IGRA methodologies and examining factors that may influence reduced cellular and humoral immune responses in similar cohorts. <strong>Disclosures:</strong> NC’s work is in part supported by an SFI grant 20/SPP/3685. The STTAR Bioresource for COVID-19 is also, in part, supported by an unrestricted grant from Takeda <br> <strong>Figure 1</strong>. Showing log IFNg levels in patients and healthy controls whole blood following stimulation with SARS CoV2 spike peptide mix. Dotted line = lower indeterminate range, Dashed line = upper indeterminate range.