Paper of the Month August 2013
Epitope engineering and molecular metrics of immunogenicity: A computational approach to VLP-based vaccine design
Vaccine. 2o13. Aug 8: http://dx.doi.org/10.1016/j.vaccine.2013.07.075 [Epub ahead of print].
H. Joshi, K. Lewis, A. Singharoy, P.J. Ortoleva
Developing antiviral vaccines is increasingly challenging due to associated time and cost of production as well as emerging drug-resistant strains. A computer-aided vaccine design strategy is presented that could greatly accelerate the discovery process and yield vaccines with high immunogenicity and thermal stability. Our strategy is based on foreign viral epitopes engineered onto well-established virus-like particles (VLPs) and demonstrates that such constructs present similar affinity for antibodies, as does a native virus. This binding affinity serves as one molecular metric of immunogenicity. As a demonstration, we engineered a preS1 epitope of hepatitis B virus (HBV) onto the EF loop of human papillomavirus VLP (HPV-VLP). HBV-associated HzKR127 antibody displayed binding affinity for this structure at distances and strengths similar to those for the complex of the antibody with the full HBV (PDBID: 2EH8). This antibody binding affinity assessment, along with other molecular immunogenicity metrics, could be a key component of a computer-aided vaccine design strategy.