Viral nanoparticles and virus-like particles: platforms for contemporary vaccine design

Abstract

Current vaccines that provide protection against infectious diseases have primarily relied on attenuated or inactivated pathogens. Virus-like particles (VLPs), comprised of capsid proteins that can initiate an immune response but do not include the genetic material required for replication, promote immunogenicity and have been developed and approved as vaccines in some cases. In addition, many of these VLPs can be used as molecular platforms for genetic fusion or chemical attachment of heterologous antigenic epitopes. This approach has been shown to provide protective immunity against the foreign epitopes in many cases. A variety of VLPs and virus-based nanoparticles are being developed for use as vaccines and epitope platforms. These particles have the potential to increase efficacy of current vaccines as well as treat diseases for which no effective vaccines are available.

Figure 1

Examples of various virus capsids that have been developed as virus‐like particle (VLP) vaccines and platforms for heterologous antigen. PDB IDS: hepatitis B capsid, 2QIJ; Papillomavirus (PV), 3IYJ;14,15 Hepatitis E virus (HEV), 2ZTN; Cowpea mosaic virus (CPMV), 1NY7; Alfalfa mosaic virus (AlMV), AMV; bacteriophage Qβ capsid, 1QBE; bacteriophage MS2–2MS2; Flock house virus (FHV) VLP, 2Q26. (Tobacco mosaic virus (TMV) image has been reprinted with permission from Ref 16. Copyright 2007 Academic Press). (Other images have been reprinted with permission from Ref 17. Copyright 2009 Oxford University Press).

Figure 2

(a) Icosahedral capsid of human papilloma virus (HPV)16 L1 capsid, PDB ID: 1DZL. (b) Electron micrograph of HPV virus‐like particles (VLPs) (Image courtesy of Merck&Co and The Scripps Research Institute). (c) L1 pentamer of HPV rendered in chimera, PDB ID: 2R5H. (d) Human hepatitis B viral capsid (HBcAg), PDB ID: 1QGT. ((a) and (d) have been reprinted with permission from Ref 17. Copyright 2009 Oxford University Press).

Figure 3

(a) Cryo‐EM reconstructions for wild‐type T4 capsid (left) and capsid with attached protective antigen fragment and N‐terminal domain of lethal factor of anthrax (right). (b) Three dimensional (*) surface shaded reconstructions of wild‐type flock house virus (FHV) (left), FHV–ANTXR2– protective antigen (PA) chimera 206 (center), and FHV–ANTXR2–PA chimera 264 (right). (c) Pseudoatomic models of FHV chimera 206 capsid protein (green) and anthrax VWA domain (yellow, left) and model including the protective antigen fragment bound to the surface (purple, right). (d) Pseudoatomic models of FHV chimera 264 capsid protein (green) and anthrax VWA domain (yellow, left) and model including the protective antigen fragment bound to the surface (purple, right). (e) Rats were immunized with FHV–ANTXR2–PA complex or controls and serum samples were collected at indicated time‐points and tested for IgG‐specific antibody responses to protective antigen. (f) Relationship between anti‐PA antibody level and survival of individual rats following challenge. ((a) has been reprinted with permission from Ref 67. Copyright 2007 Academic Press). ((b)–(f) have been reproduced with permission from Annette Schneemann Ref 65. Copyright 2007 Public Library of Science).