Mechanical tuning of virus-like particles.

HYPOTHESIS:Virus-like particles (VLPs) are promising scaffolds for developing mucosal vaccines. For their optimal performance, in addition to design parameters from an immunological perspective, biophysical properties may need to be considered. EXPERIMENTS:We investigated the mechanical properties of VLPs scaffolded on the coat protein of Acinetobacter phage AP205 using atomic force microscopy and small angle X-ray scattering. FINDINGS:Investigations showed that AP205 VLP is a tough nanoshell of stiffness 93 ± 23 pN/nm and elastic modulus 0.11 GPa. However, its mechanical properties are modulated by attaching muco-inert polyethylene glycol to 46 ± 10 pN/nm and 0.05 GPa. Addition of antigenic peptides derived from SARS-CoV2 spike protein by genetic fusion increased the stiffness to 146 ± 54 pN/nm although the elastic modulus remained unchanged. These results, which are interpreted in terms of shell thickness and coat protein net charge variations, demonstrate that surface conjugation can induce appreciable changes in the biophysical properties of VLP-scaffolded vaccines.