Effect\nof Anti-PEG Antibody on Immune Response of\nmRNA-Loaded Lipid Nanoparticles

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