Structural and Functional Analysis of Recombinant Virus-Like Particles (VLPs)

Virus-like particle (VLP) approach has been attracting more attentions in recent years for designing vaccines against infectious diseases as well as non-infectious disease targets. The first two VLP-based vaccines, RECOMBIVAX HB® and Gardasil® against hepatitis B virus and human papillomavirus, respectively, will be reviewed with respect to the structural and functional analysis. To be viable as vaccine candidates, VLPs need to be produced at reasonable cost in the commercial production scale. Robust and scale-able process using E coli has been developed for several VLP-based vaccine candidates at full production scale. As a successful example of VLP approach, the development of the first licensed human vaccine for Hepatitis E virus (HEV) infection will be reviewed with respect to the technical, clinical and regulatory milestones during its 14-year developmental cycle. Key antigenic determinants of the products were defined by the reactivity to a panel of monoclonal antibodies (mAbs). The epitope for a conformational and strongly neutralizing mAb 8C11 was mapped to individual amino acids using x-ray crystal structures in three segments of peptides on the dimeric form of ORF2 protein. Post licensure supports of HEV vaccine (Hecolin®, licensed and marketed in China) on the VLP production and quality control are outlined with a battery of biochemical, biophysical and immunochemical analyses. In addition, other promising VLP based human vaccine candidates in pre-clinical and clinical testing stage are discussed, particularly for those that are amenable to the E coli production platform.