iVAX consists of a suite of immunoinformatics tools for the design of epitope driven vaccines.
Emerging and re-emerging infectious diseases represent a significant challenge for next-generation vaccine design and bioterror preparedness. We have composed a suite of online immunoinformatics tools for accelerated design of genome-derived, epitope-driven vaccines generated from protein sequences. Using the Conservatrix algorithm, even the most mutable pathogenic genomes may be probed for highly conserved segments, which are then mapped for T cell epitopes and regions of high epitope density using EpiMatrix and ClustiMer. JanusMatrix, an improved homology analysis tool examining pathogen/host sequence similarity with respect to the HLA and TCR faces of an epitope, is used to screen out sequences which could potentially elicit an undesired autoimmune or regulatory T cell response due to homology with sequences encoded by the human genome. Immunogenic Consensus Sequences are created by EpiAssembler, a tool which optimizes the balance between pathogen and population coverage. VaccineCAD links candidate epitopes into a string-of-beads design while minimizing nonspecific junctional epitopes that may be created in the linking process.
With proof of principle established in animal models for vaccines against tularemia, Vaccinia and H. pylori, the iVAX toolkit exemplifies a rapid, efficient, easily accessible and broadly applicable solution to accelerate the development of critically important vaccines for human health and biodefense.
EpiMatrix takes overlapping 9-mer frames derived from the conserved target protein sequences and scores them for potential binding affinity against a panel of Class I or Class II HLA alleles; each frame-by-allele assessment that scores highly and is predicted to bind is a putative T cell epitope. ClustiMer takes EpiMatrix output and identifies clusters of 9-mers that contain large numbers of putative T cell epitopes. BlastiMer automates the process of submitting the previously identified sequences to BLAST to determine if any share similarities with the human genome; any such similar sequences would be likely to be tolerated or to elicit an unwanted autoimmune response. EpiAssembler takes the conserved, immunogenic sequences identified by Conservatrix and EpiMatrix and knits them together to form highly immunogenic consensus sequences.
ClustiMer screens EpiMatrix output and identifies clusters of 9-mers that contain large numbers of putative T cell epitopes.
BlastiMer automates the process of submitting the previously identified sequences to BLAST to determine if any share similarities with known proteins.
JanusMatrix is designed to predict the potential for cross reactivity between epitope clusters and the human genome, based on conservation of TCR-facing residues in their putative HLA ligands. http://www.ncbi.nlm.nih.gov/pubmed/23584251
Conservatrix parses input sequences into 9-mer strings and identifies those 9-mer sequences that are conserved amongst multiple inputted whole sequences, such as multiple strains of the same pathogen, for even the most mutable of potential vaccine targets.
EpiAssembler takes the conserved, immunogenic sequences identified by Conservatrix and EpiMatrix and knits them together to form highly immunogenic consensus sequences.
Aggregatrix is used to determine the minimum set of epitopes that will cover the maximum number of HLA types, as well as the maximum number of variations of the target pathogen.
VaccineCAD aggregates potential vaccine candidates into a string-of-beads vaccine design while minimizing any deleterious junctional epitopes that may appear in the joining process.
The effect of collecting these immunoinformatics tools, applying them to high-profile vaccine projects, and putting them in the hands of vaccine researchers will be able to accelerate the development of critically important vaccines for human health and biodefense.
- iVAX: A Sophisticated Suite of Online Vaccine Design Tools #1 – APR 2013
- iVAX: A Sophisticated Suite of Online Vaccine Design Tools #2 – Oct 2013
- More EpiVax Posters Here
- New IVax publication here.