Virus-like Particles Produced in Plants: A Promising Platform for Recombinant Vaccine Development

Abstract

The capsid proteins of many viruses are capable of spontaneous self-assembly into virus-like particles (VLPs), which do not contain the viral genome and are therefore not infectious. VLPs are structurally similar to their parent viruses and are therefore effectively recognized by the immune system and can induce strong humoral and cellular immune responses. The structural features of VLPs make them an attractive platform for the development of potential vaccines and diagnostic tools. Chimeric VLPs can be obtained by attaching foreign peptides to capsid proteins. Chimeric VLPs present multiple copies of the antigen on their surface, thereby increasing the effectiveness of the immune response. Recombinant VLPs can be produced in different expression systems. Plants are promising biofactories for the production of recombinant proteins, including VLPs. The main advantages of plant expression systems are the overall low cost and safety of plant-produced products due to the absence of pathogens common to plants and animals. This review provides an overview of the VLP platform as an approach to developing plant-produced vaccines, focusing on the use of transient expression systems.

Keywords: biofactory; plant; transient expression; vaccine; virus-like particle.

Figure 1

An overview of the transient expression of recombinant proteins in plants.

Figure 2

Some widely used plant transient expression systems. The T-DNA regions of plant expression vectors based on the genomes of turnip vein-clearing virus (TVCV) and crucifer-infecting TMV (cr-TMV) (magnICON), cowpea mosaic virus (CPMV) (pEAQ), bean yellow dwarf virus (BeYDV), and potato virus X (PVX) (pEff). RB and LB, the left and right T-DNA; target, gene of interest; Act2, Arabidopsis actin 2 promoter; 35S, the promoter of cauliflower mosaic virus RNA; Nos-T, the terminator of the A. tumefaciens nopaline synthase gene; Term, the terminator of transcription; p19, the gene of tomato bushy stunt virus silencing suppressor; LIR, long intergenic region; SIR, short intergenic region; Rep/RepA, replication proteins from BeYDV; RDRP, RNA-dependent RNA polymerase gene; Sgp1, the first promoter of subgenomic RNA of PVX; AMV, a translational enhancer from alfalfa mosaic virus; p24, the gene of grapevine leafroll-associated virus-2 silencing suppressor; 5′ and 3′, untranslated regions (of diverse origins).

Figure 3

Scheme of transient expression in plant cells using viral expression vectors.

Figure 4

General scheme of chimeric VLP formation. (a) Native VLPs; (b) chimeric VLPs obtained by genetic fusion approach; (c) chimeric VLPs obtained by chemical crosslinking in vitro.

Figure 5

The structures of HBc (PDB 6HU4). (a) Monomer chains A, B, C, and D are marked in blue, green, pink, and yellow, respectively. Three-dimensional modeling was performed by SWISS-MODEL [130]. (b) VLPs of HBc [131].