Comparative Analysis of Lipid Nanoparticles in Pfizer-BioNTech and Moderna COVID-19 Vaccines: Insights from Molecular Dynamics Simulations

COVID-19 vaccines, such as Pfizer-BioNTechs BNT162b and Modernas mRNA-1273, have demonstrated robust efficacy. However, direct comparisons of their delivery vehicles remain limited. Notably, BNT162b requires storage at -80{degrees}C, while mRNA-1273 is stored at -20{degrees}C. This discrepancy in storage temperatures may be influenced by differences in the structure and stability of the lipid nanoparticles (LNPs) used in these vaccines. Ionizable lipids, such as SM-102 in Modernas vaccine and ALC-0315 in Pfizers vaccine, play a crucial role in LNP stability and function, affecting endosomal escape, cellular uptake, and drug release. Understanding these variations is essential for optimizing vaccine delivery systems. In our study, we use molecular dynamics simulations with the coarse-grained Martini forcefield to compare the LNPs in Moderna and Pfizers COVID-19 vaccines, providing insights at an experimental scale. Our findings indicate that the ionizable lipid tail of BNT162b (ALC-0315) exhibits a higher degree of branching, resulting in a more bifurcated appearance compared to the structure of the ionizable lipids in mRNA-1273 (SM-102).