Abstract
Computational vaccinology includes epitope mapping, antigen selection, and immunogen design using computational tools. Tools that facilitate the in silico prediction of immune response to biothreats, emerging infectious diseases, and cancers can accelerate the design of novel and next generation vaccines and their delivery to the clinic. Over the past 20 years, vaccinologists, bioinformatics experts, and advanced programmers based in Providence, Rhode Island, USA have advanced the development of an integrated toolkit for vaccine design called iVAX, that is secure and user-accessible by internet. This integrated set of immunoinformatic tools comprises algorithms for scoring and triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, re-engineering or eliminating regulatory T cell epitopes, and re-designing antigens to induce immunogenicity and protection against disease for humans and livestock. Commercial and academic applications of iVAX have included identifying immunogenic T cell epitopes in the development of a T-cell based human multi-epitope Q fever vaccine, designing novel influenza vaccines, identifying cross-conserved T cell epitopes for a malaria vaccine, and analyzing immune responses in clinical vaccine studies. Animal vaccine applications to date have included viral infections of pigs such as swine influenza A, PCV2, and African Swine Fever. “Rapid-Fire” applications for biodefense have included a demonstration project for Lassa Fever and Q fever. As recent infectious disease outbreaks underscore the significance of vaccine-driven preparedness, the integrated set of tools available on the iVAX toolkit stand ready to help vaccine developers deliver genome-derived, epitope-driven vaccines.
Highlights
Over the past 20 years, academic researchers and commercial companies have developed immunoinformatics tools to discover the T cell epitope “triggers” that activate the immune system and have applied these tools to vaccine design
In a collaboration with Chris Eickhoff and Dan Hoft at Saint Louis University, we identified CD4+ and CD8+ T cell epitopes that are highly conserved in diverse influenza A strains that were shown to be immunogenic in humans expressing genetically diverse MHC [59]
Building on our experience with the “rapid fire” development of a vaccine for Lassa Fever [60], EpiMatrix and JanusMatrix were used to identify 50 promiscuous class II epitopes from Coxiella burnetii antigens that were tested in HLA binding assays and screened for immunogenicity in HLA-DR3 transgenic mice by colleagues at the Vaccines and Immunotherapy Center (VIC, Harvard) and Innatoss, Oss, the Netherlands [28, 29]
Summary
Over the past 20 years, academic researchers and commercial companies have developed immunoinformatics tools to discover the T cell epitope “triggers” that activate the immune system and have applied these tools to vaccine design. New information on cross-conservation between pathogen T cell epitopes and the human genome (and microbiome) is emerging, and has important implications for vaccine design. “memory” of cross-conserved T cell epitopes has been defined as a key contributor to the strength of protection generated by vaccines [2,3,4]. These discoveries are coming to light through the application of new tools that examine T cell epitopes and their role in vaccines, using the power of immunoinformatics
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