Abstract

Abstract 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. Pathogen sequences which could potentially elicit an undesired autoimmune or T-regulatory response due to homology with sequences encoded by the human genome are screened out using BlastiMer and JanusMatrix, an improved homology analysis tool examining pathogen/host sequence similarity with respect to the HLA and TCR faces of an epitope. Immunogenic Consensus Sequences are created by EpiAssembler, a tool which optimizes the balance between pathogen and population coverage. VaccineCAD links potential vaccine candidate epitopes into a string-of-beads design while minimizing non-specific 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.

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