The invention provides a process for the purification recombinantly expressed, self-assembled VLP from the homogenate of a bacterial host, wherein the process can be scaled up to a commercial production scale in a cost effective manner. The process comprises a first chromatography using an anion exchange matrix, a second chromatography using hydroxyapatite and, optionally, a size exclusion chromatography. VLP preparations obtained by the process of the invention are essentially free of endotoxin contaminations.

We disclose a method of obtaining a polyepitopic protein, a DNA vector for the embodiment of the method as well as polyepitopic proteins fused with macromolecular carriers. The proteins obtained according to the present invention are in a number of uses, in particular when used in the production of improved vaccines.

This invention provides a virus-like particle (VLP) that is formed by a protein of a viral origin (such as from a Hepatitis B virus) and derivatized by way of an isopeptide bond formed between two partner peptides (such as a SpyCatcher/SpyTag connection) to present on the VLP surface one or more antigenic epitopes of a target antigen. Also provided are methods of making the VLP, compositions comprising the VLP, as well as applications of the VLP and the compositions for modulating a recipient's immune response to the target antigen, including immunization against the antigen or desensitization to the antigen.