Virus-like particles (VLPs) are made up of protein monomers that self-assemble into the conformation of the native virus, but lack a viral genome. VLPs are safe and efficacious vaccine candidates since they closely mimic the native virus structure, but are not infectious. Many VLPs are composed of one or more structural proteins which assemble first into capsomeres, followed by assembly into the full VLP. Often, when monomers are expressed as a recombinant protein, the VLP does not assemble properly which results in a non-native VLP conformation. In these cases, a disassembly and reassembly step may be incorporated into the purification process in order to improve immunogenicity, homogeneity, and stability of the VLP product. In some VLPs, inter-capsomere cross-linking via disulfide bonds promote structural integrity and stability of the VLP. In this work, we examined the role of protein concentration and equipment surfaces on reassembly and cross-linking reactions in a model VLP system. A model was developed to gain better understanding of the role that trace metals, buffers, and surfaces play in promoting VLP cross-linking. Additionally, we examined how the extent of cross-linking affected VLP attributes such as stability, potency, and size. VLPs with varying levels of cross-linking were generated to study these effects.

Examining the role of metals and surfaces on VLP cross-linking and the impact on VLP stability

2019 Spring National Meeting

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