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

Lars Rønn Olsen, Guang Lan Zhang, Derin B. Keskin, Ellis L. Reinherz, Vladimir Brusic

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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. SinceT-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 areT-cell epitope candidates.

Original languageEnglish
Article numberArticle 69
JournalFrontiers in Immunology
Volume2
Issue numberDEC
DOIs
Publication statusPublished - 2011

Keywords

  • Antigenic diversity
  • Epitope-based vaccines
  • Immunoinformatics
  • Polyvalent vaccines
  • Reverse vaccinol-ogy
  • Vaccine informatics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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