Pesquisa imunológica
Acesso livre

Abstrato

Immunogenic Consensus Sequence T helper Epitopes for a Pan-Burkholderia Biodefense Vaccine

Anne S. De Groot, Matthew Ardito, Leonard Moise, Eric A. Gustafson, Denice Spero, Gloria Tejada, William Martin

Background: Biodefense vaccines against Category B bioterror agents Burkholderia pseudomallei (BPM) and Burkholderia 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 immunoinfor-matics for vaccine design. Using EpiMatrix, ClustiMer and EpiAssembler, a set of immunoinformatic vac-cine design tools, we screened the 31 available Burkholderia genomes and performed initial tests of our selections that are candidates for an epitope-based multi-pathogen vaccine against Burkholderia species. Results: Immunoinformatics analysis of 31 Burkholderia genomes yielded 350,004 9-mer candidate vaccine peptides of which 133,469 had perfect conservation across the 10 BM genomes, 175,722 had per-fect conservation across the 11 BPM genomes and 40,813 had perfect conservation across the 10 BC ge-nomes. Further screening with EpiMatrix yielded 54,010 high-scoring Class II epitopes; these were assem-bled into 2,880 longer highly conserved ‘immunogenic consensus sequence’ T helper epitopes. 100% of the peptides bound to at least one HLA class II allele in 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 multiple Burkholderia species and test their binding to HLA ligands in vitro. The next step in our process will be to test the epitopes ex vivo using 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-Burkholderia biodefense vaccine.