A systematic bioinformatics approach for selection of epitope-based vaccine targets
Asif M. Khana b, Olivo Miottob c, A. T. Heinyb, Jérôme Salmond, K.N. Srinivasand e, Eduardo J. M. Nascimentof, Ernesto T. A. Marquesd f g, Vladimir Brusića h, Tin Wee Tanb, Joseph Thomas Augustd✉
- aDepartment of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore
- bDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore
- cInstitute of Systems Science, National University of Singapore, 25 Heng Mui Keng Terrace, Singapore 119615, Singapore
- dDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
- eProduct Evaluation & Registration Division, Centre for Drug Administration, Health Sciences Authority, 11 Biopolis Way, Singapore 138667, Singapore
- fDepartment of Medicine, Division of Infectious Diseases, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
- gLaboratory of Vaccinology and Experimental Therapeutics, Aggeu Magalhaes Research Center, FIOCRUZ, Brazil
- hSchool of Land and Food Sciences, and Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
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Abstract
Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with dengue virus as a model system. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertype human leukocyte antigen (HLA) alleles. The selected sequences are tested for biological function by their activation of T-cells of HLA transgenic mice and of pathogen infected subjects. This approach provides an experimental basis for the design of pathogen specific, T-cell epitope-based vaccines that are targeted to majority of the genetic variants of the pathogen, and are effective for a broad range of differences in human leukocyte antigens among the global human population.