title: A bioinformatics tool for epitope-based vaccine design that accounts for human ethnic diversity: application to emerging infectious diseases.
abstract: BACKGROUND
  Peptide vaccination based on multiple T-cell epitopes can be used to target well-defined ethnic populations. Because the response to T-cell epitopes is restricted by HLA proteins, the HLA specificity of T-cell epitopes becomes a major consideration for epitope-based vaccine design. We have previously shown that CD4+ T-cell epitopes restricted by 95% of human MHC class II proteins can be predicted with high-specificity.
  
  
  METHODS
  We describe here the integration of epitope prediction with population coverage and epitope selection algorithms. The population coverage assessment makes use of the Allele Frequency Net Database. We present the computational platform Predivac-2.0 for HLA class II-restricted epitope-based vaccine design, which accounts comprehensively for human genetic diversity.
  
  
  RESULTS
  We validated the performance of the tool on the identification of promiscuous and immunodominant CD4+ T-cell epitopes from the human immunodeficiency virus (HIV) protein Gag. We further describe an application for epitope-based vaccine design in the context of emerging infectious diseases associated with Lassa, Nipah and Hendra viruses. Putative CD4+ T-cell epitopes were mapped on the surface glycoproteins of these pathogens and are good candidates to be experimentally tested, as they hold potential to provide cognate help in vaccination settings in their respective target populations.
  
  
  CONCLUSIONS
  Predivac-2.0 is a novel approach in epitope-based vaccine design, particularly suited to be applied to virus-related emerging infectious diseases, because the geographic distributions of the viruses are well defined and ethnic populations in need of vaccination can be determined ("ethnicity-oriented approach"). Predivac-2.0 is accessible through the website http://predivac.biosci.uq.edu.au/.
authors: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Australia; Biotechnology Centre, Universidad San Sebastián, Concepción, Chile. Electronic address: patricio.oyarzun@uss.cl.
authors: Patricio
authors: P
authors: Oyarzun
authors: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Australia.
authors: Jonathan J
authors: JJ
authors: Ellis
authors: Institute of Integrative Biology, University of Liverpool, United Kingdom.
authors: Faviel F
authors: FF
authors: Gonzalez-Galarza
authors: Institute of Integrative Biology, University of Liverpool, United Kingdom.
authors: Andrew R
authors: AR
authors: Jones
authors: Transplant Immunology Laboratory, Royal Liverpool University Hospital & School of Infection and Host Defence University of Liverpool, United Kingdom.
authors: Derek
authors: D
authors: Middleton
authors: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Australia; School of Information Technology and Electrical Engineering, University of Queensland, Queensland 4072, Australia.
authors: Mikael
authors: M
authors: Boden
authors: School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Australia. Electronic address: b.kobe@uq.edu.au.
authors: Bostjan
authors: B
authors: Kobe
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019295:Computational Biology; D015195:Drug Design; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D045404:Hendra Virus / Q000276:immunology; D045464:Henipavirus Infections / Q000276:immunology / Q000517:prevention & control; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007835:Lassa Fever / Q000276:immunology / Q000517:prevention & control; D007836:Lassa virus / Q000276:immunology; D045405:Nipah Virus / Q000276:immunology; D044469:Racial Groups / Q000235:genetics*; D022223:Vaccines, Subunit / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: Emerging infectious diseases; Immunodominance; Lassa, Nipah and Hendra viruses; MHC (HLA) class II proteins; Multi-epitope peptide vaccination