Accelerated development of a T Cell epitope-driven biodefense vaccine for Burkholderia (VAC7P.957)

Abstract

Abstract Background: Burkholderia pseudomallei (BPM) and Burkholderia mallei (BM) are Category B pathogens. Burkholderia cepaciae (BC) causes chronic lung infections in cystic fibrosis patients. We are developing an epitope-driven multi-pathogen vaccine against all three Burkholderia species. Methods: Immunoinformatics tools were used to identify immunogenic consensus sequences (ICS) that are enriched for promiscuous and highly conserved CD4+ T cell epitopes in all three Burkholderia species. Top scoring 70 ICS were tested for binding affinity to 7 Class II HLA alleles in binding assays. Immunogenicity of the ICS was tested in human PBMCs, and in Balb/C (peptide immunization) and HLA DR3 transgenic mice (DNA-prime/peptide-boost immunization). Results: 100% of the ICS bound to at least two Class II HLA alleles for which they were predicted. The immunoinformatic predictions were validated in 77.3% of the HLA-peptide binding assays. Significant IFN-γ response was induced by all peptides in at least one human donor as measured by ELISpot assay. In contrast, 28.6% and 11% of the ICS peptides elicited significant IFN-γ responses in splenocytes from vaccinated Balb/C and DR3 transgenic mice as measured by ELISpot assay, respectively. Conclusions: These results illustrate the power of immunoinformatics tools for rapid selection of highly conserved epitopes for biodefense vaccines. Differences in human and murine immune responses may be due to ineffective delivery of the vaccine immunogen.