Blood Distribution of SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine in Humans

SJ Kent; S Li; TH Amarasena; A Reynaldi; WS Lee; MG Leeming; DH O’Connor; J Nguyen; HE Kent; F Caruso; JA Juno; AK Wheatley; MP Davenport; Y Ju

Journal article

Blood Distribution of SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine in Humans

SJ Kent, S Li, TH Amarasena, A Reynaldi, WS Lee, MG Leeming, DH O’Connor, J Nguyen, HE Kent, F Caruso, JA Juno, AK Wheatley, MP Davenport, Y Ju

ACS Nano | Published : 2024

DOI: 10.1021/acsnano.4c11652

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Abstract

Lipid nanoparticle mRNA vaccines are an exciting but emerging technology used in humans. There is limited understanding of the factors that influence their biodistribution and immunogenicity. Antibodies to poly(ethylene glycol) (PEG), which is on the surface of the lipid nanoparticle, are detectable in humans and boosted by human mRNA vaccination. We hypothesized that PEG-specific antibodies could increase the clearance of mRNA vaccines. To test this, we developed methods to quantify both the vaccine mRNA and ionizable lipid in frequent serial blood samples from 19 subjects receiving Moderna SPIKEVAX mRNA booster immunization. Both the vaccine mRNA and ionizable lipid peaked in blood 1-2 day..

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University of Melbourne Researchers

Stephen Kent Author

Wen Shi Lee Author

Michael Leeming Author

Frank Caruso Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

We thank the participations for the generous involvement and provision of samples. We thank C.-J. Kim and S. Ye (University of Melbourne) for excellent technical assistance and helpful discussion. We acknowledge the Melbourne Mass Spectrometry and Proteomics Facility for provision of lipidomics services. This study was supported by the Australian Research Council (ARC) Discovery Project (DP210103114 to F.C., S.J.K., Y.J., A.K.W., and M.P.D.), the National Health and Medical Research Council (NHMRC) program grant (GNT1149990 to S.J.K. and M.P.D.), the Victorian Critical Vaccinees Collection COVID-19 Research Seed Funding Grant (Y.J.), an ARC Discovery Early Career Researcher Award (DE230101542 to Y.J.), and NHMRC Investigator grants (S.J.K.; W.S.L.; GNT2016732 to F.C.; J.A.J.; A.K.W.; and M.P.D.). For the purposes of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. Figures a and a and Table of Contents graphic were created with BioRender.com.