OP0085 LONGITUDINAL T CELL RESPONSES TO A SERIES OF FOUR SARS-COV-2 VACCINE DOSES OR COVID-19 IN PATIENTS ON TNF INHIBITORS

Background T cells are critical for control of viral infection with SARS-CoV-2, but knowledge is lacking on cellular immune responses following repeated vaccination and breakthrough in immunosuppressed patients. Objectives To examine longitudinal cell across diagnoses, vaccine series COVID-19 patients tumor necrosis factor inhibitors (TNFi). Methods The prospective, observational Nor-vaC study included arthritis (spondyloarthritis, rheumatoid arthritis, psoriatic arthritis) or inflammatory bowel disease (IBD) (ulcerative colitis, Crohns disease) immunosuppressive therapies [1]. Here, we TNFi mono- combination therapy immunised up to four SARS-CoV-2 doses without infection, collecting peripheral blood mononuclear (PBMCs) 2-4 weeks after each immunisation. Samples were incubated spike, nucleocapside membrane peptides. percentage responding was measured by flow cytometry (2) (≥0.01% increase CD4 cells, ≥0.001% CD8 compared baseline). Results Between February 2021 December 2022, 144 (monotherapy n=86 (60%), methotrexate azathioprine n=58 (40%)) (median age 48 years [IQR 33-57]; 51% women) (Table 1). proportions vs IBD 2 75% (12/16 patients) 86% (25/29), 3 83% (10/12) 93% (28/30). In total, 80% (4/5) showed further increases a 4 th dose. Conversely, 81% (13/16) vs. 55% (16/29) had two doses, 67% (8/12) 62% (18/29) three doses. A rd dose induced higher the previous (6/11) 100% (5/5) Arthritis lower than dose; median response 0.024% 0.009-0.036] 0.098% 0.040-0.182], p=0.0004; 0.003% 0.001-0.016] 0.044% 0.009-0.140], p=0.0032 (Figure This difference remained robust adjusting sex, p<0.001, no longer detected Breakthrough elicited increased all diagnoses spike (p<0.0001), nucleocapsid (p=0.002) proteins (p=0.001) unstimulated cells. Also, Spike-specific 0.18% 0.06%, p=0.003; 0.08% 0.01%, p<0.0001), lesser extent 0.12%, p=0.05; 0.05%, p=0.26). There differences between (p=0.93). Conclusion Patients show improved immunisation, generating strong broad response. significantly CD4+ These results support giving TNFi-treated patients, particular benefit References [1]Syversen S.W et al Rheumatol. 2022 [2]Kared H Nature Communications. Table 1. Number providing COVID-19. Disease, n (%) total (n=144) vaccines (n=49) (n=86) (n=44) Hybrid immunity b (n=62) 25 (17) 17 (35) 19 (22) 5 (11) (8) 119 (83) 32 (65) 67 (78) 39 (89) 57 (92) Sampled at minimum one timepoint followed Figure T-cell (V3) (V4) doses/ TNFα+ CD40L+ (% CD4+) IFNγ+ CD8+). Acknowledgements We thank health-care workers who have participated Norwegian patient representatives group, Kristin Isabella Kirkengen Espe Roger Thoresen. personnel, laboratory other staff involved departments involved, particularly Synnøve Aure, Margareth Sveinsson, May Britt Solem, Elisabeth Røssum-Haaland, Kjetil Bergsmark. Disclosure Interests Hilde Ørbo: None declared, Asia -Sophia F. M. Wolf: Hammersbøen Bjørlykke Speakers bureau: bureaus Janssen-Cilag, Sarah Josefsson: Guri Solum: Ingrid Fadum Kjønstad: Jyssum: E. Christensen: Anne Therese Tveter: Joseph Sexton: Grete B. Kro: Gunnveig Grodeland Bayer, Sanofi, ThermoFisher, Consultant of: AstraZeneca, Tore K. Kvien Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, AbbVie, Biogen, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Grant/research from: BMS MSD, UCB, Jørgen Jahnsen AbbVie/Abbott, Bristol-Myers, Squibb, Galapagos, Janssen, Roche, Takeda, Bristol-Myers Boehringer-Ingelheim, John Torgils Vaage: Espen Haavardsholm Sella Aarrestad Provan: Hassen Kared: Ludvig A. Munthe Cellgene, Kaasen Jørgensen Silje Watterdal Syversen: Siri Mjaaland: Guro Løvik Goll UCB.