Monitoring Anti-PEG Antibodies Level upon Repeated Lipid Nanoparticle-Based COVID-19 Vaccine Administration

Abstract

PEGylated lipids are one of the four constituents of lipid nanoparticle mRNA COVID-19 vaccines. Therefore, various concerns have been raised on the generation of anti-PEG antibodies and their potential role in inducing hypersensitivity reactions following vaccination or in reducing vaccine efficacy due to anti-carrier immunity. Here, we assess the prevalence of anti-PEG antibodies, in a cohort of vaccinated individuals, and give an overview of their time evolution after repeated vaccine administrations. Results indicate that, in our cohort, the presence of PEG in the formulation did not influence the level of anti-Spike antibodies generated upon vaccination and was not related to any reported, serious adverse effects. The time-course analysis of anti-PEG IgG showed no significant booster effect after each dose, whereas for IgM a significant increase in antibody levels was detected after the first and third dose. Data suggest that the presence of PEG in the formulation does not affect safety or efficacy of lipid-nanoparticle-based COVID-19 vaccines.

Keywords: COVID-19; SARS-CoV-2; anti-PEG Ig; anti-Spike Ig; lipid-nanoparticle-mRNA (LNP-mRNA)-based vaccine.

Figure 1

Vaccination schedule and blood sample collection: serum samples were collected before vaccination (d0), and seven days after each dose of vaccine (d1, d2 and d3). Vaccine schedule was I and II dose 21 days apart, and III dose 6 months following the II dose. All volunteers received BioNTech/Pfizer as t I and II dose, whereas for the III dose either BioNTech/Pfizer or a half-dose of Moderna were administered.

Figure 2

Anti-PEG antibodies following lipid nanoparticles-mRNA COVID-19 vaccination (BioNTech/Pfizer or Moderna). Anti-PEG IgG (A) and anti-PEG IgM (B) measured in heathy donors before vaccination and seven days after each vaccine dose (d0, d1, d2 and d3, respectively). Longitudinal analysis of anti-PEG IgG (C) and anti-PEG IgM (D), different colours represent different healthy donors. Kruskal–Wallis test, followed by Dunn’s post-test for multiple comparisons, was used for assessing statistical differences between groups (**** p ≤ 0.0001).

Figure 3

Comparison of anti-PEG IgG and IgM in subjects boosted with BioNTech/Pfizer or Moderna formulation. Anti-PEG IgG (A) and anti-PEG IgM (B) measured in heathy donors. All the volunteers received the BioNTech/Pfizer vaccine as the first and second doses, and then were boosted with Pfizer-BioNTech (Pfizer d3, 34.3%) or Moderna (Moderna d3, 65.7%) for the third dose. Kruskal–Wallis test, followed by Dunn’s post-test for multiple comparisons, was used for assessing statistical differences between groups (* p ≤ 0.05; **** p ≤ 0.0001).

Figure 4

Correlation analysis between anti-PEG, anti-Spike, anti-RBD antibodies and age. Multiple correlations were visualized as matrix with the Spearman’s correlation coefficient values reported. Correlation coefficients were reported with a color scale between red (direct correlation) and blue (inverse correlation) Color intensity and square size are proportional to the absolute value of Spearman correlation coefficients. Statistically significant correlations were labeled as: * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001.