TY - JOUR

T1 - Investigation of the Electrokinetic Properties of HIV-Based Virus-Like Particles

AU - Wolf, Tobias

AU - Grau, Christoph

AU - Rosengarten, Jamila Franca

AU - Stitz, Jörn

AU - Wilkens, Jan

AU - Barbe, Stéphan

N1 - Funding Information: The authors thank Beatrix Martiny and Astrid Schauss at the CECAD Cologne Imaging Facility for excellent sample preparation and electron microscopic-analysis of VLPs. This work was supported by grants from the German Federal Ministry of Education and Research, funding program Forschung an Fachhochschulen, contract numbers 13FH767IA6 to SB and JS.

PY - 2024/3/5

Y1 - 2024/3/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85186177640&partnerID=8YFLogxK

U2 - 10.1021/acs.langmuir.3c03535

DO - 10.1021/acs.langmuir.3c03535

M3 - Article

C2 - 38385169

AN - SCOPUS:85186177640

VL - 40

SP - 4762

EP - 4771

JO - LANGMUIR

JF - LANGMUIR

SN - 0743-7463

IS - 9

ER -