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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.

OriginalsprogEngelsk
TidsskriftMolecular Pharmaceutics
Vol/bind20
Udgave nummer7
Sider (fra-til)3356-3366
Antal sider11
ISSN1543-8384
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by the Novo Nordisk Foundation Grants No. NNF16OC0022166 (T.L.A.), NFF205A0063505 (P.G.), and NNF20SA0064201 (P.G.), as well as the Carlsberg Foundation (CF20-476 0045) (P.G.) and the Svend Andersen Research Foundation (SARF2021) (P.G.). The funding source was not involved in any part of the study design, data collection, data analysis, interpretation of the data, or the writing of the manuscript. The Danish COVID-19 Biobank (part of Bio- and Genome Bank Denmark) is acknowledged for biological material and for data regarding handling and storage.

Publisher Copyright:
© 2023 American Chemical Society.

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