Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

Vijayan, Veena; Mohapatra, Adityanarayan; Uthaman, Saji; Park, In-Kyu

For VLP to be used as a delivery vehicle, the target antigen from a virus different from the one used in the VLP is attached to the VLP surface; and this surface-modified VLP paves the way for its use in targeting various diseases. VLPs could be engineered to attach additional proteins on its surface, either through the fusion of proteins on the particle, or by expressing multiple antigens, which in turn protects against its source virus and other antigens present on its surface [75] . Polysaccharides and small organic molecules are non-protein antigens that can be chemically attached to the VLP surface to form bioconjugate particles [76] . The baculovirus expression system is mostly used to generate VLPs with an excellent safety profile, as baculovirus does not naturally infect human [77] . In another study, a safe and efficient VLP system based on avian retrovirus was designed such that the system was considered safe, as it could not replicate itself in human cells. This system was considered as safe because the VLP constitutes only Gag fusion protein; a single VLP could deliver about (2000-5000) copies of the Gag fusion protein into the transduced cell. In another study, VLPs were created for delivery with two different approaches: the intracellular distribution of Gag fusion proteins, or by modifying the surface of VLPs for receptor/ligand-mediated delivery ( Figure 2 ) [57] . deleted before expression. This prevents packed genome integration into the host cell, as well as the recombination of the live or defective virus. The first VLP vaccine was developed against the hepatitis B virus, which was later commercialized in 1986 [72] . VLP vaccines against hepatitis E and the human papillomavirus have been used in human since 2006 [73, 74] . VLPs can be obtained from a variety of viruses, and can have different sizes ranging (20 to 800) nm; further, they can be obtained via different processes [56] . The initial approach to obtain VLPs involves the self-assembly of capsid proteins in the expression host, followed by purification of the assembled protein to avoid contaminants that are adhered or encapsulated. However, in a few cases, for better quality and low contamination, the VLP structure needs to be disassembled and reassembled. Another emerging method to obtain VLPs is to use cell-free in vitro processing, wherein at first large-scale purification is performed to prevent contamination, and then assembly of VLP structures in vitro, to avoid their disassembly in a cell; commercialized VLPs are derived from a target virus by self-assembling its proteins.