POS0257 COMPARISON OF SARS-CoV-2 VACCINE RESPONSE IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASE; mRNA-1273 VACCINE INDUCES HIGHER HUMORAL IMMUNOGENICITY THAN BNT162b2

Abstract

BackgroundThe SARS-CoV-2 messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) have benefitted all countries amid the coronavirus disease 2019 (COVID-19) crisis. Whereas both of them have shown efficacy in preventing COVID-19 illness in healthy participants, there is paucity of data about immunogenicity and safety of mRNA COVID-19 vaccines in patients with autoimmune, inflammatory rheumatic disease. Recent observational studies evaluated mainly BNT162b2, suggesting that glucocorticoids, immunosuppressive agents impair SARS-CoV-2 vaccine responses. However, difference in immune reactions and safety between BNT162b2 and mRNA-1273 have not been clarified in patients with inflammatory rheumatic diseases.ObjectivesTo assess humoral and T cell immune responses and safety profiles after two doses of different mRNA vaccine against SARS-CoV-2; BNT162b2 and mRNA-1273.MethodsWe enrolled consecutive, previously uninfected patients with inflammatory rheumatic diseases receiving mRNA vaccine including BNT162b2 and mRNA-1273. Healthy participants receiving BNT162b2 were also recruited as control. Blood samples were obtained 3weeks, 2 months, 3 months, 4 months, and 6 months after second dose of vaccines. We measured titres of neutralizing antibodies against SARS-CoV-2 and calculated seroconversion rates to evaluate humoral responses. We also assessed T-cell immunity responses by using interferon releasing assay against SARS-CoV-2 in a part of the patients. Answers to questionnaires about adverse reactions were obtained from participants.ResultsA total of 974 patients with inflammatory rheumatic diseases and healthy 630 control participants were enrolled. Among them, 796 patients received BNT162b2, 178 patients received mRNA-1273, and all control participants received BNT162b2. Seroconversion rates and neutralizing antibody titres 3 weeks after vaccination were significantly higher in patients with mRNA-1273 and healthy participants with BNT162b2 compared with patients with BNT162b2; seroconversion rates, 97.2% vs 99.5% vs 83.3%, p<0.001; titers of neutralizing antibodies, 29.4±33.9 IU/mL vs 23.9±14.2 IU/mL vs 10.8±16.5 IU/mL, p<0.001, respectively. On another front, T cell reaction against SARS-CoV-2 was similar in both patients with mRNA-1273 and BNT162b2; interferon gamma levels for antigen 1, 1.2±2.1 IU/mL vs 0.8±2.5 IU/mL, p=0.23; and for antigen 2, 1.4±1.9 IU/mL vs 1.0±2.1 IU/mL, p=0.11, respectively. Regarding adverse reaction of each mRNA vaccine, the frequency of systemic adverse reactions including fever and general fatigue are also significantly higher in patients with mRNA-1273 and healthy controls than patients with BNT162b2; fever, 48.0% vs 44.9% vs 10.2%, p<0.001; general fatigue, 70.4% vs 61.8% vs 31.2%, p<0.001, respectively). In longitudinal measurement, neutralizing antibody titres in patients with BNT162b2 were decreased more rapidly than those in healthy controls; 3.3±3.2 IU/mL in patients with BNT162b2 at 4 months and 3.2±4.7 IU/mL in healthy controls with BNT162b2 at 6 months. We identified age, glucocorticoid dose (prednisolone > 7.5mg), use of immunosuppressants including methotrexate, mycophenolate, cyclophosphamide, and tacrolimus are associated with rapid attenuation of humoral responses in patients with BNT162b2.ConclusionOur results demonstrated a significant higher humoral immunogenicity and frequency of systemic adverse reaction of the SARS-CoV-2 mRNA-1273 (Moderna) compared with the BNT162b2 (Pfizer-BioNTech) in inflammatory rheumatic disease patients. Glucocorticoid and immunosuppressive agents impaired induction and sustention of neutralizing antibody, and earlier third booster vaccination may be required within 4 months, especially for those receiving BNT162b2.