Investigation of the Electrokinetic Properties of HIV-Based Virus-Like Particles

Abstract

The antigen density on the surface of HIV-based virus-like particles (VLPs) plays a crucial role in the improvement of HIV vaccine potency. HIV VLPs consist of a dense protein core, which is surrounded by a lipid bilayer and whose surface is usually decorated with antigenic glycoproteins. The successful downstream processing of these particles is challenging, and the high-resolution and cost-efficient purification of HIV-based VLPs has not yet been achieved. Chromatography, one of the major unit operations involved in HIV VLP purification strategies, is usually carried out by means of ion exchangers or ion-exchange membranes. Understanding the electrokinetic behavior of HIV-based VLPs may help to improve the adjustment and efficiency of the corresponding chromatographic processes. In this study, we investigated the electrokinetics and aggregation of both undecorated and decorated VLPs and interpreted the data from the perspective of the soft particle model developed by Ohshima (OSPM), which fails to fully predict the behavior of the studied VLPs. Post-Ohshima literature, and particularly the soft multilayer particle model developed by Langlet et al., provides an alternative theoretical framework to overcome the limits of the OSPM. We finally hypothesized that the electrophoretic mobility of HIV-based VLPs is controlled by an electrohydrodynamic interplay between envelope glycoproteins, lipid bilayer, and Gag envelope.