The delicate balance in genetically engineering live vaccines.
The delicate balance in genetically engineering live vaccines.
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DOI：
10.1016/j.vaccine.2013.12.026
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发表时间：
2014-07-31
期刊：
影响因子：
5.5
通讯作者：
Curtiss, Roy, III
中科院分区：
文献类型：
--
作者：
Galen, James E.;Curtiss, Roy, III
当代疫苗开发较少依赖于疫苗构建的经验方法，并且现在采用一系列强大的精确工程策略来构建免疫原性活疫苗。在这篇综述中，我们将调查用于创建减毒疫苗的各种工程技术，重点是最近的进展和见解。我们将进一步探索减毒株的适应性，以创建针对多种不相关病原体的多价疫苗平台。这些载体疫苗被设计为将足够水平的保护性抗原递送至适当的淋巴诱导位点，以引发载体特异性和外来抗原特异性免疫。尽管这些技术中的许多最初是为沙门氏菌疫苗而开发的，但这些方法的基本逻辑的应用将在可能的情况下扩展到其他肠疫苗的开发。推动我们讨论的一个中心主题将强调，工程疫苗的最终成功取决于实现减毒和免疫原性之间的适当平衡。实现这种平衡将避免过度激活炎症反应，这会导致不可接受的反应原性，但将保持足够的代谢适应性，使活疫苗能够到达深层组织诱导部位并触发保护性免疫。本文所提供的广泛的例子将清楚地表明，基因工程提供了迅速推动疫苗开发进入新的应用和疗法的潜力，这将显着扩大疫苗在公共卫生中的作用。
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.
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影响因子：
4
作者：
Galen, James E;Pasetti, Marcela F;Tennant, Sharon;Ruiz-Olvera, Patricia;Sztein, Marcelo B;Levine, Myron M
通讯作者：
Levine, Myron M
影响因子：
--
作者：
Kang, HY;Curtiss, R
通讯作者：
Curtiss, R
影响因子：
5.5
作者：
Hohmann, EL;Oletta, CA;Miller, SI
通讯作者：
Miller, SI
影响因子：
6.4
作者：
Galen, James E.;Chinchilla, Magaly;Levine, Myron M.
通讯作者：
Levine, Myron M.
影响因子：
3.1
作者：
Kong, Qingke;Yang, Jiseon;Curtiss, Roy, III
通讯作者：
Curtiss, Roy, III