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The double-edged sword: How evolution can make or break a live-attenuated virus vaccine.
Evolution ( IF 3.1 ) Pub Date : 2011-12-01 , DOI: 10.1007/s12052-011-0365-y
Kathryn A Hanley 1
Affiliation  

Even students who reject evolution are often willing to consider cases in which evolutionary biology contributes to, or undermines, biomedical interventions. Moreover the intersection of evolutionary biology and biomedicine is fascinating in its own right. This review offers an overview of the ways in which evolution has impacted the design and deployment of live-attenuated virus vaccines, with subsections that may be useful as lecture material or as the basis for case studies in classes at a variety of levels. Live- attenuated virus vaccines have been modified in ways that restrain their replication in a host, so that infection (vaccination) produces immunity but not disease. Applied evolution, in the form of serial passage in novel host cells, is a "classical" method to generate live-attenuated viruses. However many live-attenuated vaccines exhibit reversion to virulence through back-mutation of attenuating mutations, compensatory mutations elsewhere in the genome, recombination or reassortment, or changes in quasispecies diversity. Additionally the combination of multiple live-attenuated strains may result in competition or facilitation between individual vaccine viruses, resulting in undesirable increases in virulence or decreases in immunogenicity. Genetic engineering informed by evolutionary thinking has led to a number of novel approaches to generate live-attenuated virus vaccines that contain substantial safeguards against reversion to virulence and that ameliorate interference among multiple vaccine strains. Finally, vaccines have the potential to shape the evolution of their wild type counterparts in counter-productive ways; at the extreme vaccine-driven eradication of a virus may create an empty niche that promotes the emergence of new viral pathogens.

中文翻译:

双刃剑:进化如何制造或破坏减毒活病毒疫苗。

即使是拒绝进化的学生也常常愿意考虑进化生物学有助于或破坏生物医学干预的案例。此外,进化生物学和生物医学的交叉点本身就很吸引人。本综述概述了进化对减毒活病毒疫苗的设计和部署产生影响的方式,其中的小节可用作讲座材料或作为不同级别课堂案例研究的基础。减毒活病毒疫苗经过改良,可以抑制它们在宿主中的复制,因此感染(疫苗接种)会产生免疫力而不是疾病。应用进化,以在新宿主细胞中连续传代的形式,是一种产生减毒活病毒的“经典”方法。然而,许多减毒活疫苗通过减毒突变的回复突变、基因组其他地方的补偿突变、重组或重配或准种多样性的变化表现出毒力回复。此外,多种减毒活毒株的组合可能导致单个疫苗病毒之间的竞争或促进,导致毒力的不希望增加或免疫原性降低。以进化思维为基础的基因工程已经导致了许多产生减毒活病毒疫苗的新方法,这些方法包含防止恢复毒力的实质性保护措施,并且可以改善多种疫苗株之间的干扰。最后,疫苗有可能以适得其反的方式影响其野生型对应物的进化;
更新日期:2019-11-01
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