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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Natural selection for rash-forming genotypes of the varicella-zoster vaccine virus detected within immunized human hosts
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Natural selection for rash-forming genotypes of the varicella-zoster vaccine virus detected within immunized human hosts

机译：在免疫的人类宿主内检测到的水痘带状疱疹疫苗病毒形成疹子的基因型的自然选择

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The Oka vaccine strain is a live attenuated virus that is routinely administered to children in the United States and Europe to prevent chickenpox. It is effective and safe but occasionally produces a rash. The vaccine virus has accumulated mutations during its attenuation, but the rashes are not explained by their reversion, unlike complications reported for other viral vaccines. Indeed, most of the novel mutations distinguishing the Oka vaccine from the more virulent parental virus have not actually become fixed. Because the parental alleles are still present, the vaccine is polymorphic at > 30 loci and therefore contains a mixture of related viruses. The inoculation of > 40 million patients has consequently created a highly replicated evolutionary experiment that we have used to assess the competitive ability of these different viral genotypes in a human host. Using virus recovered from rash vesicles, we show that two vaccine mutations, causing amino acid substitutions in the major transactivating protein IE62, are out-competed by the ancestral alleles. Standard interpretations of varicella disease severity concentrate on the undeniably important effects of host genotype and immune status, yet our results allow us to demonstrate that the viral genotype is associated with virulence and to identify the key sites. We propose that these loci have pleiotropic effects on the immunogenic properties of the virus, rash formation, and its epidemiological spread, which mould the evolution of its virulence. These findings are of practical importance for reducing the incidence of vaccine-associated rash and promoting public acceptance of the vaccine.
机译：Oka疫苗株是一种减毒活病毒，通常在美国和欧洲的儿童中接种以预防水痘。它既有效又安全，但偶尔会出疹子。疫苗病毒在减毒过程中已经积累了突变，但是皮疹不能通过逆转来解释，这与其他病毒疫苗的并发症不同。的确，将Oka疫苗与毒性更强的父母病毒区分开来的大多数新突变实际上并未得到修复。由于亲本等位基因仍然存在，因此疫苗在> 30个位点具有多态性，因此包含相关病毒的混合物。因此，接种超过4000万患者已创建了高度重复的进化实验，我们已使用该实验评估了人类宿主中这些不同病毒基因型的竞争能力。使用从皮疹囊泡中回收的病毒，我们显示了两个疫苗突变（在主要的反式激活蛋白IE62中引起氨基酸取代）被祖先等位基因所竞争。水痘疾病严重程度的标准解释集中在宿主基因型和免疫状态的不可否认的重要影响上，但是我们的结果使我们能够证明病毒基因型与毒力有关并确定关键位点。我们建议这些基因座对病毒的免疫原性，皮疹形成及其流行病学传播具有多效性，从而影响其毒力的演变。这些发现对于降低疫苗相关皮疹的发生率并促进公众对疫苗的接受具有实际意义。

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