Broad spectrum assessment of the epitope fluctuation--Immunogenicity hypothesis.

Prediction of immunogenicity is a substantial barrier in vaccine design. Here, a molecular dynamics approach to assessing the immunogenicity of nanoparticles based on structure is presented. Molecular properties of epitopes on nonenveloped viral particles are quantified via a set of metrics. One such metric, epitope fluctuation (and implied flexibility), is shown to be inversely correlated with immunogenicity for each of a broad spectrum of nonenveloped viruses. The molecular metrics and experimentally determined immunogenicities for these viruses are archived in the open-source vaccine computer-aided design database. Results indicate the promise of computer-aided vaccine design to bring greater efficiency to traditional lab-based vaccine discovery approaches.