Bull James J, Antia Rustom
Department of Biological Sciences, University of Idaho, Moscow, ID 83844-3051, USA.
Department of Biology, Emory University, Atlanta, GA 30322, USA.
Evol Med Public Health. 2022 Apr 26;10(1):202-213. doi: 10.1093/emph/eoac015. eCollection 2022.
Theory suggests that some types of vaccines against infectious pathogens may lead to the evolution of variants that cause increased harm, particularly when they infect unvaccinated individuals. This theory was supported by the observation that the use of an imperfect vaccine to control Marek's disease virus in chickens resulted in the virus evolving to be more lethal to unvaccinated birds. This raises the concern that the use of some other vaccines may lead to similar pernicious outcomes. We examine that theory with a focus on considering the regimes in which such outcomes are expected.
We evaluate the plausibility of assumptions in the original theory. The previous theory rested heavily on a particular form of transmission-mortality-recovery trade-off and invoked other assumptions about the pathways of evolution. We review alternatives to mortality in limiting transmission and consider evolutionary pathways that were omitted in the original theory.
The regime where the pernicious evolutionary outcome occurs is narrowed by our analysis but remains possible in various scenarios. We propose a more nuanced consideration of alternative models for the within-host dynamics of infections and for factors that limit virulence. Our analysis suggests imperfect vaccines against many pathogens will not lead to the evolution of pathogens with increased virulence in unvaccinated individuals.
Evolution of greater pathogen mortality driven by vaccination remains difficult to predict, but the scope for such outcomes appears limited. Incorporation of mechanistic details into the framework, especially regarding immunity, may be requisite for prediction accuracy.
A virus of chickens appears to have evolved high mortality in response to a vaccine that merely prevented disease symptoms. Theory has predicted this type of evolution in response to a variety of vaccines and other interventions such as drug treatment. Under what circumstances is this pernicious result likely to occur? Analysis of the theory in light of recent changes in our understanding of viral biology raises doubts that medicine-driven, pernicious evolution is likely to be common. But we are far from a mechanistic understanding of the interaction between pathogen and host that can predict when vaccines and other medical interventions will lead to the unwanted evolution of more virulent pathogens. So, while the regime where a pernicious result obtains may be limited, caution remains warranted in designing many types of interventions.
理论表明，某些针对传染性病原体的疫苗可能会导致危害性增加的变异体的进化，尤其是当这些病原体感染未接种疫苗的个体时。这一理论得到了以下观察结果的支持：使用一种不完善的疫苗来控制鸡的马立克氏病病毒，导致该病毒进化后对未接种疫苗的禽类更具致死性。这引发了人们对使用其他一些疫苗可能导致类似有害后果的担忧。我们对该理论进行了研究，重点关注预期会出现此类结果的情况。
我们评估了原理论中假设的合理性。先前的理论严重依赖于一种特定形式的传播 - 死亡率 - 恢复权衡，并援引了关于进化途径的其他假设。我们审视了限制传播过程中死亡率的替代因素，并考虑了原理论中遗漏的进化途径。
我们的分析缩小了出现有害进化结果的情况范围，但在各种情形下仍有可能发生。我们建议对感染的宿主内动态以及限制毒力的因素的替代模型进行更细致入微的考量。我们的分析表明，针对许多病原体的不完善疫苗不会导致未接种疫苗个体中病原体毒力增加的进化。
由疫苗驱动的病原体更高死亡率的进化仍然难以预测，但此类结果出现的可能性似乎有限。将机制细节纳入框架，尤其是关于免疫方面的细节，对于预测准确性可能是必要的。
一种鸡病毒似乎因一种仅能预防疾病症状的疫苗而进化出了高致死率。理论预测，针对各种疫苗以及其他干预措施（如药物治疗）会出现这种类型的进化。在何种情况下可能会出现这种有害结果呢？根据我们对病毒生物学理解的最新变化对该理论进行分析后，人们对医学驱动的有害进化可能普遍存在产生了怀疑。但我们距离对病原体与宿主之间相互作用的机制性理解还很远，这种理解能够预测疫苗和其他医学干预何时会导致更具毒力的病原体出现不良进化。所以，虽然出现有害结果的情况可能有限，但在设计多种类型的干预措施时仍需谨慎。
