Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools

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.

New Immunoinformatics Tools for Swine: Designing Epitope-Driven Vaccines, Predicting Vaccine Efficacy, and Making Vaccines on Demand

“…A wide range of tools have been developed in the past 20 years that dramatically accelerate the design of novel and next generation vaccines. In a recent publication, we have described the utility of iVAX for human vaccine design and analysis ( 4 ). Here we will focus on the integration of PigMatrix into a pre-existing toolkit, and describe applications of the combined tools to swine vaccines.…”

“…It is an interactive internet-based platform that integrates user input, immunoinformatics algorithms and several sequence databases, enabling users to rapidly identify and triage candidate antigens, select immunogenic T cell epitopes, eliminate potential regulatory T cell epitopes, and optimize antigens for immunogenicity and protection against disease. Detailed descriptions of the tools are published [see references ( 4 , 6 – 8 )]. While the tools were designed for humans, swapping out the tools used for epitope prediction from Human Leukocyte Antigen (HLA) to Swine Leukocyte Antigen (SLA) has enabled EpiVax vaccine developers to apply these advanced tools to infectious disease problems affecting swine.…”

“…This tool accepts sequence input for human, swine, and murine major hisotocompatability complex (MHC) class I and class II epitope prediction. The generated predictions can then be incorporated into further analysis using a variety of tools including the Conservatrix, ClustiMer , EpiAssembler ( 4 ) and VaxCAD algorithms ( 10 ). Conservatrix enables a search for sequences across variable pathogens, for example, swine influenza A, or Porcine Reproductive and Respiratory Syndrome Virus (PRRSV).…”

“…T cell epitope mapping algorithms enable the analysis of complete proteomes of any size to identify vaccine candidates for experimental validation. Despite the demonstrated utility of computational vaccinology in human vaccine development ( 4 ), computational tools for vaccine design are very limited for non-human species. This is mainly due to the limitations on available experimental data that is required to develop prediction models.…”

Insights from the comparison of genomic variants from two influenza B viruses grown in the presence of human antibodies in cell culture

“…In addition to expanding the range of current vaccines, new vaccines using novel approaches are being developed. Bioinformatic tools are being used to identify epitopes which can be developed into vaccines for influenza A [ 38 , 39 ]. Epitopes for M2 and NP proteins been identified as vaccine candidates and are being developed [ 37 , 40 ].…”