Persistence of SARS-CoV-2 neutralizing antibodies and anti-Omicron IgG induced by BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic disease: an explanatory study in Japan

Yuta Yamaguchi; Shinichiro Nameki; Yasuhiro Kato; Ryotaro Saita; Tomoharu Sato; Sayaka Nagao; Teruaki Murakami; Yuko Yoshimine; Saori Amiya; Takayoshi Morita; Yasutaka Okita; Takahiro Kawasaki; Jun Fujimoto; Yasutaka Ueda; Yuichi Maeda; Akane Watanabe; Hyota Takamatsu; Sumiyuki Nishida; Yoshihito Shima; Masashi Narazaki; Atsushi Kumanogoh

doi:10.1016/j.lanwpc.2022.100661

Persistence of SARS-CoV-2 neutralizing antibodies and anti-Omicron IgG induced by BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic disease: an explanatory study in Japan

Lancet Reg Health West Pac. 2023 Mar:32:100661. doi: 10.1016/j.lanwpc.2022.100661. Epub 2022 Dec 20.

Authors

Yuta Yamaguchi^{1

2}, Shinichiro Nameki^{1

2}, Yasuhiro Kato^{1

2}, Ryotaro Saita³, Tomoharu Sato⁴, Sayaka Nagao⁵, Teruaki Murakami^{1

2}, Yuko Yoshimine^{1

2}, Saori Amiya^{1

2}, Takayoshi Morita^{1

2}, Yasutaka Okita^{1

2}, Takahiro Kawasaki^{1

2}, Jun Fujimoto^{1

2}, Yasutaka Ueda⁶, Yuichi Maeda^{1

7}, Akane Watanabe^{1

8}, Hyota Takamatsu^{1

2}, Sumiyuki Nishida¹, Yoshihito Shima^{1

8}, Masashi Narazaki^{1

9}, Atsushi Kumanogoh^{1

2

5

7

10

11}

Affiliations

¹ Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
² Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Japan.
³ Department of Medical Innovation, Osaka University Hospital, Suita, Japan.
⁴ Department of Biostatistics and Data Science, Graduate School of Medicine, Osaka University, Suita, Japan.
⁵ Center for Infectious Diseases for Education and Research (CiDER), Osaka University, Suita, Japan.
⁶ Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Japan.
⁷ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Japan.
⁸ Laboratory of Thermo-Therapeutics for Vascular Dysfunction, Graduate School of Medicine, Osaka University, Suita, Japan.
⁹ Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
¹⁰ Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Osaka University, Osaka, Japan.
¹¹ Center for Advanced Modalities and DDS (CAMaD), Osaka University, Osaka, Japan.

Abstract

Background: Autoimmune inflammatory rheumatic disease (AIRD) patients are at high risk of the coronavirus disease 2019 (COVID-19), but the medium-term effects of immunosuppressants on vaccine efficacy are unknown. We investigated the duration of humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and Omicron variant in AIRD patients administered with two doses of the BNT162b2 (Pfizer-BioNTech) vaccine.

Methods: Serum-neutralizing antibody (NAb) and anti-receptor-binding domain (RBD)/spike antibody levels were measured. Short- and medium-term effects of immunosuppressants were analyzed pre-vaccination (Term 1) and 14-42 days (Term 2) and 100-200 days (Term 3) after the second vaccination.

Findings: From Feb 1, 2021, to Feb 28, 2022, 439 AIRD patients and 146 healthy controls were investigated. The seropositivity rate and log₁₀-NAb titers were significantly lower in AIRD patients than in controls at Terms 2 and 3. In rheumatoid arthritis patients, tumor necrosis factor-α inhibitors (TNFis) at Term 3, and older age, glucocorticoids, and abatacept at Terms 2 and 3 were risk factors for reduced responses. Anti-Omicron RBD/spike IgG levels strongly correlated with NAb titers.

Interpretation: Glucocorticoids, TNFis, and abatacept treatments negatively affect the longevity of humoral responses to SARS-CoV-2, including Omicron, after two vaccine doses. These findings may inform the timing of additional vaccination for AIRD patients.

Funding: Cloud Funding of Peace Winds Japan; Center of Innovation Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science KAKENHI; Japan Agency for Medical Research and Development; Kansai Economic Federation; Mitsubishi Zaidan; and Research Grant from Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology.

Keywords: Autoimmune inflammatory rheumatic disease; BNT162b2 mRNA vaccine; Humoral response; SARS-CoV-2; SARS-CoV-2 Omicron variant.