mRNA-LNP Vaccine(Tsinghua University)

Messenger RNA (mRNA) vaccines using lipid nanoparticles (LNPs) are globally approved with acceptable safety profiles for preventing respiratory diseases. Here, we describe tissue distribution and kinetics of mRNA-LNP vaccines after intramuscular dosing using three products formulated with same LNP matrix: mRNA-1273 (Spikevax), mRNA-1647 (a candidate cytomegalovirus [CMV] vaccine), and a reporter mRNA (nascent peptide-luciferase) drug product. Consistent biodistribution patterns were observed: tissues with highest exposures were the injection site, draining lymph nodes, and spleen, with minimal distribution to other organs. Levels of vaccine components declined rapidly in circulation and tissues, with model-based projections indicating concentrations at low or below quantifiable levels by ∼2 weeks. Unbound (free) spike protein was transient after mRNA-1273 vaccination (modeled decline < 5 days) and did not accumulate with repeated dosing. The ionizable lipid in the LNP, lipid H, underwent biotransformation and was excreted renally and hepatically, with no human-specific metabolites. Collectively, these results indicate similar biodistribution patterns across products within this dataset using a shared LNP composition, despite different mRNA cargo. Furthermore, in a SARS-CoV-2 infection-free model, no sustained spike protein was observed. Overall, the data establish a framework that can be used to scientifically justify leveraging data across a shared platform.