Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens.
Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens.
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DOI：
10.1371/journal.pbio.1002198
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发表时间：
2015-07
期刊：
影响因子：
9.8
通讯作者：
Nair VK
中科院分区：
文献类型：
--
作者：
Read AF;Baigent SJ;Powers C;Kgosana LB;Blackwell L;Smith LP;Kennedy DA;Walkden-Brown SW;Nair VK
一些疫苗能驱动更致命的病原体的进化吗？传统观点认为，如果宿主的死亡大大减少了传播，自然选择将消除高致命性的病原体。因此，保持宿主存活但仍允许传播的疫苗可能会使毒性很强的菌株在人群中传播。在这里，我们实验表明，鸡对马立克氏病病毒的免疫增强了更强毒株的适应性，使高致病性毒株传播成为可能。通过直接接种或通过母体接种引起的免疫可延长宿主存活，但不能防止感染、病毒复制或传播，从而延长毒株的感染期，否则毒株太致命而不能持续。我们的数据表明，不能防止传播的抗病疫苗可能会创造条件，促进病原体菌株的出现，从而在未接种疫苗的宿主中引起更严重的疾病。一项在家禽中使用马立克氏病病毒的研究表明，通过减少对高毒力毒株的自然选择，不完善的疫苗接种使病毒株传播，否则这些病毒株将过于致命而无法持续。有一种理论预期认为，某些类型的疫苗可能会促使更致命（“更热”）的病原体的进化。这一观点来自于自然选择去除那些“热”到杀死宿主从而杀死自己的病原体菌株的概念。让宿主存活但不能阻止病原体传播的疫苗放松了这种选择，允许更热病原体的进化发生。这种类型的疫苗通常被称为泄漏疫苗。当疫苗阻止传播时，就像几乎所有用于人类的疫苗一样，这种向增强毒力的进化被阻止了。但是，当疫苗泄漏时，至少允许一些病原体传播，它们可以创造生态条件，使热菌株出现并持续存在。这一理论在十多年前首次提出时被证明是非常有争议的，但在这里，我们报告了在家禽中进行的马立克氏病病毒实验，这些实验表明，现代商业泄漏疫苗恰恰可以产生这种效果：它们允许病毒株向前传播，否则太致命而无法持续。因此，使用泄漏疫苗可以促进病原体菌株的进化，使未接种疫苗的宿主面临更大的严重疾病风险。未来的挑战是确定是否有其他类型的疫苗用于动物和人类，也可能产生这些进化风险。
Could some vaccines drive the evolution of more virulent pathogens? Conventional wisdom is that natural selection will remove highly lethal pathogens if host death greatly reduces transmission. Vaccines that keep hosts alive but still allow transmission could thus allow very virulent strains to circulate in a population. Here we show experimentally that immunization of chickens against Marek's disease virus enhances the fitness of more virulent strains, making it possible for hyperpathogenic strains to transmit. Immunity elicited by direct vaccination or by maternal vaccination prolongs host survival but does not prevent infection, viral replication or transmission, thus extending the infectious periods of strains otherwise too lethal to persist. Our data show that anti-disease vaccines that do not prevent transmission can create conditions that promote the emergence of pathogen strains that cause more severe disease in unvaccinated hosts. A study using Marek's disease virus in poultry shows that by reducing natural selection against highly virulent strains, imperfect vaccination enables the spread of viral strains that would otherwise be too lethal to persist. There is a theoretical expectation that some types of vaccines could prompt the evolution of more virulent (“hotter”) pathogens. This idea follows from the notion that natural selection removes pathogen strains that are so “hot” that they kill their hosts and, therefore, themselves. Vaccines that let the hosts survive but do not prevent the spread of the pathogen relax this selection, allowing the evolution of hotter pathogens to occur. This type of vaccine is often called a leaky vaccine. When vaccines prevent transmission, as is the case for nearly all vaccines used in humans, this type of evolution towards increased virulence is blocked. But when vaccines leak, allowing at least some pathogen transmission, they could create the ecological conditions that would allow hot strains to emerge and persist. This theory proved highly controversial when it was first proposed over a decade ago, but here we report experiments with Marek’s disease virus in poultry that show that modern commercial leaky vaccines can have precisely this effect: they allow the onward transmission of strains otherwise too lethal to persist. Thus, the use of leaky vaccines can facilitate the evolution of pathogen strains that put unvaccinated hosts at greater risk of severe disease. The future challenge is to identify whether there are other types of vaccines used in animals and humans that might also generate these evolutionary risks.