chapter  9
44 Pages

Construction of Novel Vaccines on the Basis of Virus-Like Particles: Hepatitis B Virus Proteins as Vaccine Carriers

Food and Drug Administration’s (FDA)-approved vaccines against hepatitis B and human papilloma viruses represent genetically engineered virus-like particles (VLPs) generated in heterologous expression systems. VLP-based vaccines are also being developed against malaria, HIV=AIDS, hepatitis C, human and avian influenza, as well as against other diseases. Moreover, VLPs from almost all classes of viruses are being evaluated now or have just been adopted to use as a scaffold for presentation of foreign immunological epitopes on the surface of chimeric VLPs. Two major strategies have been used to present foreign protein epitopes on the surface of VLPs. They are (1) classical gene fusion techniques and (2) chemical coupling of epitope peptides to the VLP surface. VLP technologies possess obvious advantages for generation of safe and efficacious vaccines. First, the repetitive antigenic structure of VLPs makes them highly immunogenic. Second, ‘‘classical’’ VLPs are lacking viral genomes or genes and are noninfectious, although they are mimicking infectious viruses in their structural and immunological features. Third, VLPs are generated by highly efficient heterologous expression of the cloned viral structural genes with subsequent quantitative in vivo or in vitro self-assembly of their products. Fourth, VLPs can be obtained by simple and efficient purification procedures. A broad range of viral structural proteins is able to form ‘‘autologous’’ VLPs consisting solely of structural protein(s) of the target virus. Many of them have been tested successfully for the construction of chimeric VLPs retaining their VLPforming ability, but carrying foreign epitopes. VLP technologies allow the generation of (1) uniform chimeric VLPs consisting of identical fusion protein subunits, (2) mosaic VLPs consisting of carrier and fusion protein subunits, and (3) pseudotyped VLPs consisting of nonfused autologous and foreign proteins. VLPs can be used for a broad range of applications, but first of all for vaccine development. In this respect, generation of vaccines against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is of special interest.