Dynamic Light Scattering Detects Reproducible Process-Associated Shifts in Virus-Like Particle Size Profiles

Virus-like particles (VLPs) are complex nanoscale structures whose physicochemical characteristics can be affected by processing conditions. Particle-size distribution is therefore an informative parameter for monitoring the physical state and consistency of VLP preparations. In this study, dynamic light scattering (DLS) was evaluated as a rapid method for comparative characterization of VLP size profiles. Ten VLP preparations were analyzed using a Malvern Zetasizer, with seven replicate measurements performed for each preparation. The dominant intensity-weighted particle-size maximum ranged from 111.5 to 165.9 nm across the complete dataset. Within-preparation coefficients of variation ranged from 1.7% to 5.7%, indicating good repeatability of the measurements. Three matched pairs representing two defined processing states were available for direct comparison. In all three pairs, a consistent shift of the dominant particle-size maximum toward smaller diameters was observed: from 141.4 to 113.5 nm, from 150.0 to 113.1 nm, and from 149.9 to 117.0 nm. These changes corresponded to decreases of 19.7%, 24.6%, and 22.0%, respectively, with a mean relative shift of 22.1%. The results show that DLS can detect reproducible process-associated changes in the physical size profile of VLP preparations. Thus, DLS may serve as a rapid complementary tool for process development, comparability assessment, and routine physicochemical characterization of VLP-based biopharmaceuticals.