Engineering virus-like particles as vaccine platforms

Abstract

Virus-like particles (VLPs) have been utilized as vaccine platforms to increase the immunogenicity of heterologous antigens. A variety of diverse VLP types can serve as vaccine platforms, and research has focused on engineering VLPs to improve their efficacy as vaccines, enhance their stability, and allow for more versatile display of antigens. Here, we review selected VLP vaccine platforms, highlight efforts to improve these platforms through structure-informed rational design, and point to areas of future research that will assist in these efforts.

Figure 1

Engineering VLP platforms for improved utility. The bacteriophage MS2 coat protein dimer is shown here as an example of engineering to improve the utility of a VLP platform. (A) The MS2 coat protein dimer is normally assembled from two identical monomers that come together such that their N- and C- termini are juxtaposed (red and blue). However, peptide insertions displayed in the surface exposed AB loop (cyan) are not tolerated, and VLPs generally do not form. (B) Engineering the coat protein monomers into a single-chain dimer (covalent fusion of two monomers) allows proper folding and VLP formation by stabilizing the dimer. (C) Foreign peptides can then be inserted into the AB loop of the down-stream coat protein copy, allowing display on the surface of the VLP (90 copies total). (D) Naturally occurring, surface-exposed amino acids with reactive groups can be utilized for conjugation of foreign antigen (here, surface exposed lysines on MS2 coat protein are shown). (E) Alternatively, the VLP can be engineered to contain amino acids with reactive groups (cysteines or lysines), sortase target sequences, etc. to allow convenient sites for conjugation of antigen post-VLP formation.