iVAX consists of a suite of immunoinformatics tools for the design of epitope driven vaccines generated from protein sequences. The immunoinformatic tools include Conservatrix, EpiMatrix, ClustiMer, BlastiMer, EpiAssembler, Aggregatrix, and VaccineCAD. 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. 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. 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. We firmly believe that 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.
