This article is part of the supplement: Selected Articles on Computational Vaccinology
Genome-wide prediction of vaccine targets for human herpes simplex viruses using Vaxign reverse vaccinology
1 Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
2 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
3 Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
4 Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
BMC Bioinformatics 2013, 14(Suppl 4):S2 doi:10.1186/1471-2105-14-S4-S2Published: 8 March 2013
Herpes simplex virus (HSV) types 1 and 2 (HSV-1 and HSV-2) are the most common infectious agents of humans. No safe and effective HSV vaccines have been licensed. Reverse vaccinology is an emerging and revolutionary vaccine development strategy that starts with the prediction of vaccine targets by informatics analysis of genome sequences. Vaxign (http://www.violinet.org/vaxign webcite) is the first web-based vaccine design program based on reverse vaccinology. In this study, we used Vaxign to analyze 52 herpesvirus genomes, including 3 HSV-1 genomes, one HSV-2 genome, 8 other human herpesvirus genomes, and 40 non-human herpesvirus genomes. The HSV-1 strain 17 genome that contains 77 proteins was used as the seed genome. These 77 proteins are conserved in two other HSV-1 strains (strain F and strain H129). Two envelope glycoproteins gJ and gG do not have orthologs in HSV-2 or 8 other human herpesviruses. Seven HSV-1 proteins (including gJ and gG) do not have orthologs in all 40 non-human herpesviruses. Nineteen proteins are conserved in all human herpesviruses, including capsid scaffold protein UL26.5 (NP_044628.1). As the only HSV-1 protein predicted to be an adhesin, UL26.5 is a promising vaccine target. The MHC Class I and II epitopes were predicted by the Vaxign Vaxitop prediction program and IEDB prediction programs recently installed and incorporated in Vaxign. Our comparative analysis found that the two programs identified largely the same top epitopes but also some positive results predicted from one program might not be positive from another program. Overall, our Vaxign computational prediction provides many promising candidates for rational HSV vaccine development. The method is generic and can also be used to predict other viral vaccine targets.