The application of virus-like particles as vaccines and biological vehicles

Abstract

Virus-like particles (VLPs) can be spontaneously self-assembled by viral structural proteins under appropriate conditions in vitro while excluding the genetic material and potential replication probability. In addition, VLPs possess several features including can be rapidly produced in large quantities through existing expression systems, highly resembling native viruses in terms of conformation and appearance, and displaying repeated cluster of epitopes. Their capsids can be modified via genetic insertion or chemical conjugation which facilitating the multivalent display of a homologous or heterogeneous epitope antigen. Therefore, VLPs are considered as a safe and effective candidate of prophylactic and therapeutic vaccines. VLPs, with a diameter of approximately 20 to 150 nm, also have the characteristics of nanometer materials, such as large surface area, surface-accessible amino acids with reactive moieties (e.g., lysine and glutamic acid residues), inerratic spatial structure, and good biocompatibility. Therefore, assembled VLPs have great potential as a delivery system for specifically carrying a variety of materials. This review summarized recent researches on VLP development as vaccines and biological vehicles, which demonstrated the advantages and potential of VLPs in disease control and prevention and diagnosis. Then, the prospect of VLP biology application in the future is discussed as well.

Keywords: Diagnostic technology; Drug delivery; VLPs; Vaccine; Virus-like particles.

Fig. 1

Virus-like particles (VLPs) mimic the overall structure of virus particles, are recognized readily by the immune system, and present viral antigens in a similar pathway to authentic conformation inducing strong immune responses

Fig. 2

A schematic diagram of the classification of different virus-like particles based on the number of viral surface proteins and the existence of lipid envelopes or not (adapted from Lua et al. 2014). For non-enveloped VLPs: (a) the single layered non-enveloped VLPs assembled by one protein (e.g., hepatitis B core antigen VLPs (Roose et al. 2013) and CPV VP2-VLPs (Xu et al. 2014)); (b) The single-layered non-enveloped VLPs assembled by two proteins (e.g., SARS coronavirus VLPs (Mortola and Roy 2004)); (c) Two-layered non-enveloped VLPs assembled by two proteins (e.g., papillomavirus L1 and L2 VLPs (McKee et al. 2015)); And (d) twolayered non-enveloped VLPs assembled by multiple proteins (e.g., FMDV-VLPs (Guo et al. 2013)); (e)The triple-layered VLPs assembled by multiple proteins (e.g., bluetongue virus (Stewart et al. 2013) and rotavirus VLPs (Parez et al. 2006)). For enveloped VLPs: (f) single-layered VLPs consisted of one protein (e.g., influenza virus ectodomain of matrix protein 2 (M2e) VLPs (Lee et al. 2014)); (g) Single-layered VLPs consisted of two protein (e.g., hantaviruses VLPs (Acuna et al. 2013)); (h) Two-layered VLPs consisted of two protein (e.g., hepatitis C VLPs (Bellier and Klatzmann 2013)), and (i) Two-layered VLPs consisted of multiple proteins (e.g., SARS coronavirus VLPs (Ho et al. 2004))

Fig. 3

Production process of VLPs derived from enveloped or nonenveloped through spontaneous self-assembling

Fig. 4

A schematic representation of assembly VLPs derived from enveloped or nonenveloped viruses which are efficient nanocarriers for cargo delivery