iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines

Abstract

Computational vaccine design, also known as computational vaccinology, encompasses epitope mapping, antigen selection and immunogen design using computational tools. The iVAX toolkit is an integrated set of tools that has been in development since 1998 by De Groot and Martin. It comprises a suite of immunoinformatics algorithms for triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, eliminating regulatory T cell epitopes, and optimizing antigens for immunogenicity and protection against disease. iVAX has been applied to vaccine development programs for emerging infectious diseases, cancer antigens and biodefense targets. Several iVAX vaccine design projects have had success in pre-clinical studies in animal models and are progressing toward clinical studies. The toolkit now incorporates a range of immunoinformatics tools for infectious disease and cancer immunotherapy vaccine design. This article will provide a guide to the iVAX approach to computational vaccinology.

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

“…We found that immune response to T cell epitopes was inversely correlated with their degree of cross-reactivity with the human genome in a subsequent study of H7N9 peptides [43]. Examining more than 4,000 published human T cell epitopes (from the Immune Epitope Database, IEDB, http://www.iedb.org/), we recently determined that the JanusMatrix "homology" score is significantly higher (p<0.0001) for T cell epitopes shown to induce regulatory cytokine (IL-10) response (N=3,780 epitopes), and significantly lower (p<0.01) for T cell epitopes shown to induce effector cytokine (IL-4) response (N=1,433 epitopes) [14]. Thus large-scale analysis of published T cell epitopes in public databases has provided additional confirmation for the hypothesis that epitope-redundancy deviate the phenotype of T cell-mediated immune responses.…”

“…Most T cell epitope mapping tools evaluate the amino acid sequence of each input 9-mer peptide (derived from the set of overlapping 9-mer sequences in any protein antigen) to a set of binding coefficients that define the propensity of the sequence to bind to HLA. On an overall scale, proteins carrying more putative epitopes would expected to be more immunogenic while proteins carrying fewer putative epitopes would tend to be less immunogenic [14]. On a local scale, T-cell epitopes (class II-restricted in particular) are not randomly distributed throughout protein sequences but instead tend to "cluster" in specific regions, and are known as promiscuous T cell epitopes [52].…”

“…In this article, we will specifically focus on T cell epitope redundancy, as defined below, which is one of the direct results of the TCR training on self in the thymus [11] and education of these T cells in the periphery [12]. Our focus on cross-reactivity of T cell epitopes is enabled by the development of accurate computational tools for the identification of these epitopes [13,14] and enlivened by reports associating autoimmune diseases to exposure to pathogens, such as the recent report linking narcolepsy to influenza exposure or vaccination [15].…”

Immunogenicity Prediction by VaxiJen: A Ten Year Overview

“…iVAX is an integrated set of tools for triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, eliminating regulatory T cell epitopes, and optimizing antigens for immunogenicity and protection against disease [187]. iVAX has been applied to vaccine development programs for emerging infectious diseases, cancer antigens and biodefense targets.…”

8th vaccine renaissance: A creative nexus for vaccine developers

“…2 Rose et al discuss the choice of the adjuvant during vaccine design and demonstrate that while the adjuvants do increase the innate response in mice injected with piggyBac plasmids, no adjuvant increases the level of transfection of the antigen. 3 Moise et al 4 describes the iVAX suite of tools along with their applications for the design of vaccines for Tularemia, Smallpox, H. Pylori, Burkholderia, HCV, Lassa virus or H1N1 and H7N9. Eickhoff et al describe the immunoinformatic strategy and in vivo validation of the identification of 30 epitopes that could be used in the design of Chagas disease vaccine.…”