2. Academic Validation
  3. Investigating Generation of Antibodies against the Lipid Nanoparticle Vector Following COVID-19 Vaccination with an mRNA Vaccine

Investigating Generation of Antibodies against the Lipid Nanoparticle Vector Following COVID-19 Vaccination with an mRNA Vaccine

  • Mol Pharm. 2023 Mar 23. doi: 10.1021/acs.molpharmaceut.2c01036.
Rasmus Münter 1,  Erik Sørensen 2,  Rasmus B Hasselbalch 3,  Esben Christensen 1,  Susanne D Nielsen 4 5,  Peter Garred 4 6,  Sisse R Ostrowski 2 4,  Henning Bundgaard 4 7,  Kasper K Iversen 3 4 8,  Thomas L Andresen 1,  Jannik B Larsen 1
Affiliations

Affiliations

  • 1 Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark (DTU), Kgs. Lyngby 2800, Denmark.
  • 2 Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark.
  • 3 Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Copenhagen 2100, Denmark.
  • 4 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  • 5 Viru-immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark.
  • 6 Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark.
  • 7 Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark.
  • 8 Department of Emergency Medicine, Copenhagen University Hospital Herlev and Gentofte, Copenhagen 2100, Denmark.
PMID: 36952227 DOI: 10.1021/acs.molpharmaceut.2c01036
Abstract

Despite the success of mRNA-based vaccines against infectious diseases (including COVID-19), safety concerns have been raised relating to the lipid nanoparticles (LNPs) used to deliver the mRNA cargo. Antibodies against the polyethylene glycol (PEG) coating on these non-viral vectors are present in the general population and can in some instances induce allergic reactions. Furthermore, treatment with PEGylated therapeutics may increase the plasma concentration of such anti-PEG Antibodies. The widespread use of PEGylated nanoparticles for mRNA vaccines concerns researchers and clinicians about a potential rise in future cases of allergic reactions against mRNA vaccines and cross-reactions with other PEGylated therapeutics. To determine if vaccination with Comirnaty increased the plasma concentration of Antibodies against LNPs, we investigated the blood plasma concentration of anti-LNP Antibodies in healthy individuals before and after vaccination with the mRNA-based COVID-19 vaccine Comirnaty (BNT162b2). Blood samples were acquired from 21 healthy adults before vaccination, 3-4 weeks after the first vaccination dose but before the second dose, and 2-6 months after the second (booster) dose. The blood plasma concentration of Antibodies recognizing the LNPs was analyzed using a microscopy-based assay capable of measuring antibody-binding to individual authentic LNPs. No significant increase in anti-LNP Antibodies was observed after two doses of Comirnaty. The LNPs used for intramuscular delivery of mRNA in the vaccine against COVID-19, Comirnaty, do, therefore, not seem to induce the generation of anti-vector Antibodies.

Keywords

COVID-19; anti-drug antibody; lipid nanoparticle; mRNA vaccine; poly(ethylene glycol); side effects.

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