Abstract
This commentary presents a Quantitative Systems Pharmacology (QSP) framework designed to support the development and optimization of mRNA vaccines. The model integrates the early events following vaccine administration—including nanoparticle uptake, antigen expression, innate immune cell recruitment, and antigen presentation—with the downstream activation of adaptive immune responses and antibody production. Through sensitivity analysis, the authors identify key vaccine properties influencing immunogenicity and show that optimizing delivery-system characteristics, such as cellular uptake and immune-cell recruitment, may have a greater impact on antibody responses than increasing antigen expression alone. The study highlights how QSP models can be used as in silico tools to compare vaccine formulations, guide optimization strategies, and support go/no-go decisions during vaccine development, ultimately helping to reduce development time, cost, and attrition rates.