Engineering Virus-like Particles for Antigen and Drug Delivery

Abstract

Virus-like particles (VLPs) are nanoscale biological structures consisting of viral proteins assembled in a morphology that mimic the native virion but do not contain the viral genetic material. The possibility of chemically and genetically modifying the proteins contained within VLPs makes them an attractive system for numerous applications. As viruses are potent immune activators as well as natural delivery vehicles of genetic materials to their host cells, VLPs are especially well suited for antigen and drug delivery applications. Despite the great potential, very few VLP designs have made it through clinical trials. In this review, we will discuss the challenges of developing VLPs for antigen and drug delivery, strategies being explored to address these challenges, and the genetic and chemical approaches available for VLP engineering.

Improvements in chemical carriers of proteins and peptides

“…The most common covalent bond was designed by the heterobifunctional chemical cross-linkers with amine and sulfhydryl-reactive arms (Shirbaghaee and Bolhassani, 2016;Hill et al, 2018). Antigens could be linked to VLPs through covalent or non-covalent bonds known as chimeric VLP (cVLPs) leading to the induction of immune responses against foreign protein epitopes.…”

“…Antigens could be linked to VLPs through covalent or non-covalent bonds known as chimeric VLP (cVLPs) leading to the induction of immune responses against foreign protein epitopes. Some chimeric VLP vaccines have been used in clinical trials including the anti-HIV p17/p24: Ty VLP, the nicotine-Qb VLP, the anti-influenza A M2-HBcAg VLP vaccine, the anti-Ang II Qb VLP, and the HBcAg VLPs displaying malaria epitopes (Shirbaghaee and Bolhassani, 2016;Hill et al, 2018). The most common covalent bond was designed by the heterobifunctional chemical cross-linkers with amine and sulfhydryl-reactive arms (Shirbaghaee and Bolhassani, 2016;Hill et al, 2018).…”

“…Generally, the chimeric VLPs were generated by genetically linkage or chemically conjugation of antigens (e.g., protein epitopes) to VLPs. The most common covalent bond was designed by the heterobifunctional chemical cross-linkers with amine and sulfhydryl-reactive arms (Shirbaghaee and Bolhassani, 2016;Hill et al, 2018). For instance, cysteine-containing antigens could be conjugated to lysine residues of VLP surface.…”

“…For instance, cysteine-containing antigens could be conjugated to lysine residues of VLP surface. Moreover, the non-covalent conjugation strategy Improvements in chemical carriers of proteins A. Bolhassani included the specific interactions of biotinylated antigens and VLPs using streptavidin as a linker (Shirbaghaee and Bolhassani, 2016;Hill et al, 2018). SV40 VLPs also encapsulated different compounds such as proteins and DNA as antigens for stimulation of adaptive immunity.…”

“…In addition, SV40 VLPs induced innate immunity as a natural adjuvant. Some chimeric VLP vaccines have been used in clinical trials including the anti-HIV p17/p24: Ty VLP, the nicotine-Qb VLP, the anti-influenza A M2-HBcAg VLP vaccine, the anti-Ang II Qb VLP, and the HBcAg VLPs displaying malaria epitopes (Shirbaghaee and Bolhassani, 2016;Hill et al, 2018).…”