Kennedy David A, Read Andrew F
Center for Infectious Disease Dynamics, Departments of Biology and Entomology, The Pennsylvania State University, University Park, PA, USA.
Center for Infectious Disease Dynamics, Departments of Biology and Entomology, The Pennsylvania State University, University Park, PA, USA
Proc Biol Sci. 2017 Mar 29;284(1851). doi: 10.1098/rspb.2016.2562.
Why is drug resistance common and vaccine resistance rare? Drugs and vaccines both impose substantial pressure on pathogen populations to evolve resistance and indeed, drug resistance typically emerges soon after the introduction of a drug. But vaccine resistance has only rarely emerged. Using well-established principles of population genetics and evolutionary ecology, we argue that two key differences between vaccines and drugs explain why vaccines have so far proved more robust against evolution than drugs. First, vaccines tend to work prophylactically while drugs tend to work therapeutically. Second, vaccines tend to induce immune responses against multiple targets on a pathogen while drugs tend to target very few. Consequently, pathogen populations generate less variation for vaccine resistance than they do for drug resistance, and selection has fewer opportunities to act on that variation. When vaccine resistance has evolved, these generalities have been violated. With careful forethought, it may be possible to identify vaccines at risk of failure even before they are introduced.
为什么耐药性普遍而疫苗抗性罕见？药物和疫苗都会对病原体群体施加巨大压力，促使其进化出抗性，事实上，耐药性通常在药物引入后不久就会出现。但疫苗抗性却很少出现。运用成熟的群体遗传学和进化生态学原理，我们认为疫苗和药物之间的两个关键差异解释了为何到目前为止疫苗在抵御进化方面比药物更具稳健性。首先，疫苗倾向于预防性起作用，而药物倾向于治疗性起作用。其次，疫苗倾向于诱导针对病原体上多个靶点的免疫反应，而药物倾向于针对极少的靶点。因此，病原体群体产生的疫苗抗性变异比耐药性变异少，而且选择作用于这种变异的机会也更少。当疫苗抗性进化时，这些普遍规律就被打破了。经过深思熟虑，甚至在疫苗引入之前就有可能识别出有失败风险的疫苗。
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