2. Academic Validation
  3. Effect of Anti-PEG Antibody on Immune Response of mRNA-Loaded Lipid Nanoparticles

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

  • Mol Pharm. 2024 Nov 4;21(11):5672-5680. doi: 10.1021/acs.molpharmaceut.4c00628.
Daiki Omata 1,  Eigo Kawahara 2 3,  Lisa Munakata 1,  Hiroki Tanaka 4,  Hidetaka Akita 4 5,  Yasuo Yoshioka 2 3 6 7 5,  Ryo Suzuki 1
Affiliations

Affiliations

  • 1 Laboratory of Drug and Gene Delivery Research, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 173-8605, Japan.
  • 2 Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 3 Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 4 Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai City, Miyagi 980-8578, Japan.
  • 5 Center for Advanced Modalities and DDS, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 6 Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 7 Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
PMID: 39324825 DOI: 10.1021/acs.molpharmaceut.4c00628
Abstract

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.

Keywords

anti-PEG antibody; lipid nanoparticle; mRNA; polyethylene glycol; vaccine.

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