Humoral immune response against SARS-CoV-2 and polyethylene glycol elicited by anti-SARS-CoV-2 mRNA vaccine, and effect of pre-existing anti-polyethylene glycol antibody in patients with hematological and autoimmune diseases
Taiki Hori,
Taro Shimizu,
Hidenori Ando,
Naoto Okada,
Hiroki Yamagami,
Saya Yasui,
Minae Hosoki,
Akihiro Tojima,
Toshiki Otoda,
Tomoyuki Yuasa,
Ken-ichi Aihara,
Makoto Takishita,
Sumiko Yoshida,
Masahiro Abe,
Tatsuhiro Ishida,
Shingen Nakamura
Affiliations
Taiki Hori
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan
Taro Shimizu
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
Hidenori Ando
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
Naoto Okada
Pharmacy Department, Yamaguchi University Hospital, Yamaguchi, Japan
Hiroki Yamagami
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan; Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
Saya Yasui
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan
Minae Hosoki
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan
Akihiro Tojima
Department of Rheumatology, Anan Medical Center, Tokushima, Japan
Toshiki Otoda
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan; Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
Tomoyuki Yuasa
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan; Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
Ken-ichi Aihara
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan; Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
Makoto Takishita
Department of Internal Medicine, Anan Medical Center, Tokushima, Japan
Sumiko Yoshida
Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan; Department of Clinical Research, National Hospital Organization Shikoku Medical Center for Children and Adults, Kagawa, Japan
Masahiro Abe
Department of Hematology, Kawashima Hospital, Tokushima, Japan
Tatsuhiro Ishida
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
Shingen Nakamura
Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan; Corresponding author. Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
Background: The effects of vaccination are modified by hematological and autoimmune diseases and/or treatment. Anti-SARS-CoV-2 mRNA vaccine contains polyethylene glycol (PEG), it is largely unknown whether PEG influences the effects of vaccination or induces a humoral response. This study examined whether anti-PEG antibodies before vaccination (pre-existing) influenced the acquisition of SARS-CoV-2 antibodies and evaluated the relationship between the development of anti-SARS-CoV-2 antibodies and anti-PEG antibodies after SARS-CoV-2 vaccination in hematological and autoimmune diseases. Methods: Anti-SARS-CoV-2 antibody IgG, anti-PEG IgG, and IgM titers were evaluated in patients with hematological and autoimmune diseases after the second dose of BNT162B2. Anti-PEG IgG and IgM titers were also measured before vaccination to examine changes after vaccination and the relationship with vaccine efficacy. Results: In patients with hematological (n = 182) and autoimmune diseases (n = 96), anti-SARS-CoV-2 and anti-PEG antibody titers were evaluated after a median of 33 days from 2nd vaccination. The median anti-SARS-CoV-2 antibody titers were 1901 AU/mL and 3832 AU/mL in patients with hematological and autoimmune disease, respectively. Multiple regression analysis showed that age and days from 2nd vaccination were negatively associated with anti-SARS-CoV-2 antibody titers. Anti-CD20 antibody treatment was negatively correlated with anti-SARS-CoV-2 antibody titers in hematological disease, and C-reactive protein (CRP) was positively correlated with anti-SARS-CoV-2 antibody titers in autoimmune disease. Baseline anti-PEG antibody titers were significantly higher in patients with autoimmune disease but were not correlated with anti-SARS-CoV-2 antibody titers. Patients with increased anti-PEG IgG acquired higher anti-SARS-CoV-2 antibody titers in patients with autoimmune disease. Conclusions: Anti-SARS-CoV-2 antibody acquisition was suboptimal in patients with hematological disease, but both anti-SARS-CoV-2 antibody and anti-PEG IgG were acquired in patients with autoimmune disease, reflecting robust humoral immune response. Pre-existing anti-PEG antibody titers did not affect anti-SARS-CoV-2 antibody acquisition.
