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

Abstract

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.

Keywords: Anti-CD20 antibody; Anti-polyethylene glycol antibody; Autoimmune disease; COVID-19; Hematological disease; mRNA vaccine.

Fig. 1

Humoral response against SARS-CoV-2 mRNA vaccination in hematological and autoimmune diseases (a) Antibody titers against anti-SARS-CoV-2 obtained by vaccination in hematological and autoimmune diseases. (b) Antibody titers by age in hematological disease (c) Antibody titers by days from second vaccination in hematological disease (d) Antibody titers in patients with hematological disease with or without anti-CD20 antibody therapy within the last 6 months. (e) Antibody titers in autoimmune disease by age. (f) Antibody titers in autoimmune disease by days from second vaccination.

Fig. 2

(a) Anti-PEG IgM antibody titers before vaccination in hematological and autoimmune diseases. (b) Anti-PEG IgG antibody titers before vaccination in hematological and autoimmune diseases. (c) The association between anti-PEG IgM before vaccination and anti-SARS-CoV-2 IgG titers obtained after vaccination in hematological disease. (d) The association between anti-PEG IgG before vaccination and anti-SARS-CoV-2 IgG titers obtained after vaccination in hematological disease. (e) The association between anti-PEG IgM before vaccination and anti-SARS-CoV-2 IgG titers obtained after vaccination in autoimmune disease. (f) The association between anti-PEG IgG before vaccination and anti-SARS-CoV-2 IgG titers obtained after vaccination in autoimmune disease.