Galen James E, Curtiss Roy
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Vaccine. 2014 Jul 31;32(35):4376-4385. doi: 10.1016/j.vaccine.2013.12.026. Epub 2013 Dec 23.
Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.
当代疫苗开发较少依赖于疫苗构建的经验方法，现在采用了一系列强大的精确工程策略来构建免疫原性活疫苗。在本综述中，我们将概述用于创建减毒疫苗的各种工程技术，重点是近期的进展和见解。我们将进一步探讨减毒株的改造，以创建用于针对多种不相关病原体进行免疫的多价疫苗平台。这些载体疫苗经过工程设计，能够将足够水平的保护性抗原递送至适当的淋巴诱导部位，以引发载体特异性和外源抗原特异性免疫。尽管这些技术中的许多最初是为沙门氏菌疫苗开发的，但这些方法的基本逻辑将尽可能扩展到其他肠道疫苗的开发中。推动我们讨论的一个核心主题将强调，工程疫苗的最终成功取决于在减毒和免疫原性之间实现适当的平衡。实现这种平衡将避免炎症反应过度激活，这会导致不可接受的反应原性，但将保留足够的代谢适应性，以使活疫苗能够到达深部组织诱导部位并触发保护性免疫。本文给出的广泛实例将清楚地表明，基因工程为迅速推动疫苗开发进入新的应用和疗法提供了潜力，这将显著扩大疫苗在公共卫生中的作用。
