Bowick Gavin C, Barrett Alan D T
Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, and Institute of Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
J Biomed Biotechnol. 2010;2010:236528. doi: 10.1155/2010/236528. Epub 2010 Jun 6.
Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.
开发针对生物威胁因子的疫苗在发现、临床前开发和许可方面面临诸多挑战。由于需要高度隔离以处理活病原体，这限制了使用完整病原体进行研究的数量和类型，而小市场则降低了行业的潜在回报。然而，从分子水平上病毒株的比较发病机制到新颖的计算方法等一系列工具，正被用于理解病毒减毒的基础并表征保护性免疫反应。随着基础分子知识的不断增加，我们不仅能够利用这些工具合理地减毒候选疫苗的病毒株，还能在计算机上评估免疫原性和安全性。本综述讨论了对发病机制的基本理解，结合系统生物学和机器学习方法，如何能够影响生物防御疫苗学。
