Original Research ARTICLE

Front. Immunol., 20 December 2011 | http://dx.doi.org/10.3389/fimmu.2011.00069

Conservation analysis of dengue virus T-cell epitope-based vaccine candidates using peptide block entropy

Lars Rønn Olsen1,2, Guang Lan Zhang1, Derin B. Keskin3,4, Ellis L. Reinherz1,3,4 and Vladimir Brusic1,3*
  • 1 Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA, USA
  • 2 Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark
  • 3 Department of Medicine, Harvard Medical School, Boston, MA, USA
  • 4 Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA, USA

Broad coverage of the pathogen population is particularly important when designing CD8+ T-cell epitope vaccines against viral pathogens. Traditional approaches are based on combinations of highly conserved T-cell epitopes. Peptide block entropy analysis is a novel approach for assembling sets of broadly covering antigens. Since T-cell epitopes are recognized as peptides rather than individual residues, this method is based on calculating the information content of blocks of peptides from a multiple sequence alignment of homologous proteins rather than using the information content of individual residues. The block entropy analysis provides broad coverage of variant antigens. We applied the block entropy analysis method to the proteomes of the four serotypes of dengue virus (DENV) and found 1,551 blocks of 9-mer peptides, which cover 99% of available sequences with five or fewer unique peptides. In contrast, the benchmark study by Khan et al. (2008) resulted in 165 conserved 9-mer peptides. Many of the conserved blocks are located consecutively in the proteins. Connecting these blocks resulted in 78 conserved regions. Of the 1551 blocks of 9-mer peptides 110 comprised predicted HLA binder sets. In total, 457 subunit peptides that encompass the diversity of all sequenced DENV strains of which 333 are T-cell epitope candidates.

Keywords: antigenic diversity, epitope-based vaccines, immunoinformatics, polyvalent vaccines, reverse vaccinology, vaccine informatics

Citation: Olsen LR, Zhang GL, Keskin DB, Reinherz EL and Brusic V (2011) Conservation analysis of dengue virus T-cell epitope-based vaccine candidates using peptide block entropy. Front. Immun. 2:69. doi: 10.3389/fimmu.2011.00069

Received: 16 August 2011; Accepted: 14 November 2011;
Published online: 20 December 2011.

Edited by:

Michael Dustin, NYU School of Medicine, USA

Reviewed by:

Christopher E. Rudd, University of Cambridge, UK
Brian M. Baker, University of Notre Dame, USA

Copyright: © 2011 Olsen, Zhang, Keskin, Reinherz and Brusic. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

*Correspondence: Vladimir Brusic, Cancer Vaccine Center, Dana-Farber Cancer Institute, Harvard Institutes of Medicine 401, 77 Avenue Louis Pasteur, Boston, MA 02118, USA. e-mail: vladimir_brusic@dfci.harvard.edu