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

Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools
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DOI:
10.3389/fimmu.2020.00442
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发表时间:
2020-04-07
影响因子:
7.3
通讯作者:
Martin, William D.
Martin, William D.
中科院分区:
医学2区
文献类型:
--
作者:
De Groot, Anne S.;Moise, Leonard;Martin, William D.

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计算疫苗学包括使用计算工具的表位作图、抗原选择和免疫原设计。促进对生物威胁、新兴传染病和癌症的免疫反应的计算机预测的工具可以加速新型和下一代疫苗的设计及其向临床的交付。在过去的20年里,位于美国罗得岛的普罗维登斯的疫苗学家、生物信息学专家和高级程序员已经推进了称为iVAX的疫苗设计集成工具包的开发,该工具包是安全的并且用户可以通过互联网访问。这套集成的免疫信息学工具包括用于对候选抗原进行评分和分类、选择免疫原性和保守的T细胞表位、重新工程化或消除调节性T细胞表位以及重新设计抗原以诱导免疫原性和针对人类和牲畜的疾病的保护的算法。iVAX的商业和学术应用包括在基于T细胞的人多表位Q热疫苗的开发中鉴定免疫原性T细胞表位、设计新型流感疫苗、鉴定疟疾疫苗的交叉保守T细胞表位以及分析临床疫苗研究中的免疫应答。迄今为止,动物疫苗的应用包括猪的病毒感染,如猪流感A,PCV2和非洲猪瘟。“速射”在生物防御方面的应用包括一个针对拉沙热和Q热的示范项目。由于最近的传染病爆发强调了疫苗驱动的准备工作的重要性,iVAX工具包上提供的一套集成工具随时准备帮助疫苗开发人员提供基因组衍生的表位驱动的疫苗。
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.