COMPARISON of SARS-COV-2 VACCINE RESPONSE in PATIENTS with INFLAMMATORY RHEUMATIC DISEASE;MRNA-1273 VACCINE INDUCES HIGHER HUMORAL IMMUNOGENICITY THAN BNT162B2

ABSTRACT

Background: The SARS-CoV-2 messenger RNA (mRNA) vaccines BNT162b2 (Pfzer-BioNTech) and mRNA-1273 (Moderna) have beneftted 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, infammatory 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 clarifed in patients with infammatory rheumatic diseases. Objectives: To 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. Methods: We enrolled consecutive, previously uninfected patients with infam-matory 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. Results: A total of 974 patients with infammatory 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 signifcantly higher in patients with mRNA-1273 and healthy participants with BNT162b2 compared with patients with BNT162b2;seroconver-sion 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 signifcantly 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 identifed 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. Conclusion: Our results demonstrated a signifcant higher humoral immuno-genicity and frequency of systemic adverse reaction of the SARS-CoV-2 mRNA-1273 (Moderna) compared with the BNT162b2 (Pfzer-BioNTech) in infammatory 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.