Development and Characterization of an In Vitro Cell-Based Assay to Predict Potency of mRNA–LNP-Based Vaccines

Messenger RNA (mRNA) vaccines have emerged as a flexible platform for vaccine development. The evolution of lipid nanoparticles effective delivery vehicles modified mRNA encoding antigens was demonstrated by the response to COVID-19 pandemic. ability rapidly develop SARS-CoV-2 from spike protein genome, and then manufacture multibillions doses per year an extraordinary achievement milestone. Further development application this additional pathogens is clearly interest. This comes with associated need new analytical tools that can accurately predict performance these candidates tie them immune expected in humans. Described here characterization imaging based vitro assay able quantitate transgene expression efficiency, utility measure (LNP)-encapsulated potency, efficacy, stability. Multiple biologically relevant adherent cell lines were screened identify suitable substrate capable providing wide dose–response curve dynamic range. Biologically attributes examined optimized, including monolayer morphology, antigen kinetics, sensitivity LNP properties, such polyethylene glycol-lipid (or PEG–lipid) composition, mass, size. Collectively, study presents strategy quickly optimize robust cell-based potency future mRNA-based vaccines.