In Vivo Blood Kinetics and Transcript Integrity of Three mRNA–Lipid Nanoparticle Vaccines in Humans
8 affiliations
- 1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia
- 2Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3000, Australia
- 3Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Heidelberg, Victoria 3084, Australia
- 4School of Science, RMIT University, Melbourne, Victoria 3000, Australia
- 5Infection Analytics Program, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, New South Wales 2052, Australia
- 6Melbourne Mass Spectrometry and Proteomics Facility, the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia
- 7Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia
- 8Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
Abstract
mRNA–lipid nanoparticle (LNP) vaccines are detectable in human blood after vaccination, but platform-specific differences in systemic persistence and transcript integrity remain poorly defined. We analyzed serial blood samples from 73 participants receiving Moderna mRNA-1273 (three formulations), Pfizer/BioNTech BNT162b2, or an investigational receptor-binding domain (RBD) mRNA vaccine (three different doses). Using droplet digital polymerase chain reaction (ddPCR) assays, we quantified total and long-range linked (“intact”) vaccine mRNA, and we measured vaccine-specific ionizable lipids by liquid chromatography–mass spectrometry (LC–MS). Across platforms, mRNA decay was fastest for mRNA-1273, intermediate for BNT162b2, and slowest for the RBD vaccine, with ionizable lipid decay following the same rank order. Notably, intact spike mRNA declined 2-fold faster after mRNA-1273 than BNT162b2 vaccination. Kinetics modeling revealed platform-dependent coupling of mRNA and lipid kinetics: intact mRNA tracked closely with SM-102 for mRNA-1273, whereas ALC-0315 persisted longer than intact mRNA for BNT162b2. A ten-fragment linkage ddPCR panel spanning the spike transcript showed lower linkage toward 3′-proximal regions that mirrored the administered mRNA-1273 formulation. Together, these data provide a quantitative framework for benchmarking mRNA–LNP platform kinetics and transcript integrity in humans.
Related
- From Formulation Quality to Anti-Tumor Immunity: A Multimodal Imaging and Translational Framework for mRNA–Lipid Nanoparticle Cancer Vaccines in Preclinical Tumor Models
- Integrated differential transcript usage and transcript abundance analyses reveal isoform-level remodeling in clear cell renal cell carcinoma
- H3K4me3-dependent transcript elongation drives hypoxia-enhanced zygotic genome activation
- A Hepatitis B virus pregenomic RNA based minigene transcript utilizes polypyrimidine tract binding protein regulated NXF1-NXT1 nuclear export pathway
- SpaCut: Transcript-Aware Morphology Fusion for Robust Cell Segmentation in Subcellular Spatial Transcriptomics.
BibTeX
@article{kent2026vivo,
title = {{In Vivo Blood Kinetics and Transcript Integrity of Three mRNA–Lipid Nanoparticle Vaccines in Humans}},
author = {Stephen J. Kent and Shiyao Li and Thakshila H. Amarasena and Arnold Reynaldi and Michael G. Leeming and Jennifer A. Juno and Adam K. Wheatley and Georgia Deliyannis and Dale I. Godfrey and Terry Nolan and Colin W. Pouton and Miles P. Davenport and Yi Ju},
journal = {ACS Nano},
year = {2026},
month = oct,
doi = {10.1021/acsnano.6c09226},
url = {https://doi.org/10.1021/acsnano.6c09226},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - In Vivo Blood Kinetics and Transcript Integrity of Three mRNA–Lipid Nanoparticle Vaccines in Humans
AU - Stephen J. Kent
AU - Shiyao Li
AU - Thakshila H. Amarasena
AU - Arnold Reynaldi
AU - Michael G. Leeming
AU - Jennifer A. Juno
AU - Adam K. Wheatley
AU - Georgia Deliyannis
AU - Dale I. Godfrey
AU - Terry Nolan
AU - Colin W. Pouton
AU - Miles P. Davenport
AU - Yi Ju
PY - 2026
DA - 2026/10/15
JO - ACS Nano
DO - 10.1021/acsnano.6c09226
UR - https://doi.org/10.1021/acsnano.6c09226
AB - mRNA–lipid nanoparticle (LNP) vaccines are detectable in human blood after vaccination, but platform-specific differences in systemic persistence and transcript integrity remain poorly defined. We analyzed serial blood samples from 73 participants receiving Moderna mRNA-1273 (three formulations), Pfizer/BioNTech BNT162b2, or an investigational receptor-binding domain (RBD) mRNA vaccine (three different doses). Using droplet digital polymerase chain reaction (ddPCR) assays, we quantified total and long-range linked (“intact”) vaccine mRNA, and we measured vaccine-specific ionizable lipids by liquid chromatography–mass spectrometry (LC–MS). Across platforms, mRNA decay was fastest for mRNA-1273, intermediate for BNT162b2, and slowest for the RBD vaccine, with ionizable lipid decay following the same rank order. Notably, intact spike mRNA declined 2-fold faster after mRNA-1273 than BNT162b2 vaccination. Kinetics modeling revealed platform-dependent coupling of mRNA and lipid kinetics: intact mRNA tracked closely with SM-102 for mRNA-1273, whereas ALC-0315 persisted longer than intact mRNA for BNT162b2. A ten-fragment linkage ddPCR panel spanning the spike transcript showed lower linkage toward 3′-proximal regions that mirrored the administered mRNA-1273 formulation. Together, these data provide a quantitative framework for benchmarking mRNA–LNP platform kinetics and transcript integrity in humans.
SN - 1936-0851
SN - 1936-086X
ER -