title: Immunogenic Consensus Sequence T helper Epitopes for a Pan-BurkholderiaBiodefense Vaccine.
abstract: BACKGROUND
  Biodefense vaccines against Category B bioterror agentsBurkholderia pseudomallei(BPM) andBurkholderia mallei(BM) are needed, as they are both easily accessible to terrorists and have strong weaponization potential.Burkholderia cepaciae(BC), a related pathogen, causes chronic lung infections in cystic fibrosis patients. Since BPM, BM and BC are all intracellular bacteria, they are excellent targets for T cell-based vaccines. However, the sheer volume of available genomic data requires the aid of immunoinformatics for vaccine design. Using EpiMatrix, ClustiMer and EpiAssembler, a set of immunoinformatic vaccine design tools, we screened the 31 availableBurkholderiagenomes and performed initial tests of our selections that are candidates for an epitope-based multi-pathogen vaccine againstBurkholderiaspecies.
  
  
  RESULTS
  Immunoinformatics analysis of 31Burkholderiagenomes yielded 350,004 9-mer candidate vaccine peptides of which 133,469 had perfect conservation across the 10 BM genomes, 175,722 had perfect conservation across the 11 BPM genomes and 40,813 had perfect conservation across the 10 BC genomes. Further screening with EpiMatrix yielded 54,010 high-scoring Class II epitopes; these were assembled into 2,880 longer highly conserved 'immunogenic consensus sequence' T helper epitopes. 100% of the peptides bound to at least one HLA class II allelein vitro, 92.7% bound to at least two alleles, 82.9% to three, and 75.6% of the binding results were consistent with the immunoinformatics analysis.
  
  
  CONCLUSIONS
  Our results show it is possible to rapidly identify promiscuous T helper epitopes conserved across multipleBurkholderiaspecies and test their binding to HLA ligandsin vitro. The next step in our process will be to test the epitopesex vivousing peripheral leukocytes from BC, BPM infected humans and for immunogenicity in human HLA transgenic mice. We expect that this approach will lead to development of a licensable, pan-Burkholderiabiodefense vaccine.
authors.affiliation: EpiVax 146 Clifford St, Providence, RI 02903, USA ; Institute for Immunology and Informatics, University of Rhode Island, 80 Washington St., Providence, RI 02903, USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.affiliation: EpiVax 146 Clifford St, Providence, RI 02903, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ardito
authors.affiliation: EpiVax 146 Clifford St, Providence, RI 02903, USA ; Institute for Immunology and Informatics, University of Rhode Island, 80 Washington St., Providence, RI 02903, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, 80 Washington St., Providence, RI 02903, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Gustafson
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, 80 Washington St., Providence, RI 02903, USA.
authors.forename: Denice
authors.initials: D
authors.lastname: Spero
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island, 80 Washington St., Providence, RI 02903, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Tejada
authors.affiliation: EpiVax 146 Clifford St, Providence, RI 02903, USA.
authors.forename: William
authors.initials: W
authors.lastname: Martin