Recombinant vector vaccine evolution
Recombinant vector vaccine evolution
复制标题
DOI：
10.1371/journal.pcbi.1006857
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发表时间：
2019-07-01
影响因子：
4.3
通讯作者：
Antia, Rustom
中科院分区：
文献类型：
--
作者：
Bull, James J.;Nuismer, Scott L.;Antia, Rustom
复制重组载体疫苗由经工程化以表达来自外源转基因的抗原的完全感受态病毒载体骨架组成。从病毒复制的角度来看，转基因不仅是有害的，甚至可能是有害的。因此，在疫苗生产过程中以及在宿主感染过程中，缺失或缺失转基因的疫苗回复突变体可能进化为主导疫苗病毒群体。一个特别的问题是，这种疫苗的进化可能会降低其抗原性--转基因引起的免疫力。我们使用数学和计算模型来研究疫苗的进化和免疫力。这些模型包括生产过程中产生的进化、疫苗和回复突变体生长的动力学，以及感染过程中引发的先天性和适应性免疫。虽然疫苗进化的选择性基础很容易理解，但免疫学后果却不容易理解。一个复杂的问题是，疫苗进化的机会受到病毒种群被清除之前宿主内生长的短期限制。更不明显的是，回复突变体的生长可能仅对宿主中的疫苗生长产生微弱干扰，因此对疫苗免疫力的影响有限。总的来说，我们发现宿主内疫苗进化有时会损害疫苗免疫力，但只有当疫苗生产过程中的进化程度严重时，这种进化才能很容易地避免或减轻。
Replicating recombinant vector vaccines consist of a fully competent viral vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be detrimental. Thus vaccine revertants that delete or inactivate the transgene may evolve to dominate the vaccine virus population both during the process of manufacture of the vaccine as well as during the course of host infection. A particular concern is that this vaccine evolution could reduce its antigenicity-the immunity elicited to the transgene. We use mathematical and computational models to study vaccine evolution and immunity. These models include evolution arising during the process of manufacture, the dynamics of vaccine and revertant growth, plus innate and adaptive immunity elicited during the course of infection. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that the opportunity for vaccine evolution is limited by the short period of within-host growth before the viral population is cleared. Even less obvious, revertant growth may only weakly interfere with vaccine growth in the host and thus have a limited effect on immunity to vaccine. Overall, we find that within-host vaccine evolution can sometimes compromise vaccine immunity, but only when the extent of evolution during vaccine manufacture is severe, and this evolution can be easily avoided or mitigated.