Effect of Anti-PEG Antibody on Immune Response of mRNA-Loaded Lipid Nanoparticles

Lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccines have been approved for use to combat coronavirus disease 2019 (COVID-19). The mRNA-LNPs contain PEG-conjugated lipids. Clinical studies have reported that mRNA-LNPs induce the production of anti-PEG antibodies, but the anti-PEG antibodies do not affect the production of neutralizing antibodies. However, the detailed influence of anti-PEG antibodies on mRNA-LNP vaccines remains unclear. Therefore, in this study, we prepared ovalbumin (OVA) as a model antigen-encoding mRNA-loaded LNP (mRNA-OVA-LNP), and we determined whether anti-PEG antibodies could affect the antigen-specific immune response of mRNA-OVA-LNP vaccination in mice pretreated with PEG-modified liposomes to induce the production of anti-PEG antibodies. After intramuscular (i.m.) injection of the mRNA-LNP, the anti-PEG antibodies did not change the expression of protein or induction of cytokine and cellular immune response but did slightly increase the induction of antigen-specific antibodies. Furthermore, repeated mRNA-LNP i.m. injection induced the production of anti-PEG IgM and anti-PEG IgG. Our results suggest that mRNA-LNP induces the production of anti-PEG antibodies, but the priming of the antigen-specific immune response of mRNA-LNP vaccination is not notably affected by anti-PEG antibodies.