Pathogenicity testing of influenza candidate vaccine viruses in the ferret model
Pathogenicity testing of influenza candidate vaccine viruses in the ferret model
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DOI：
10.1016/j.virol.2017.08.024
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发表时间：
2017-11-01
期刊：
影响因子：
3.7
通讯作者：
Tumpey, Terrence M.
中科院分区：
文献类型：
--
作者：
Belser, Jessica A.;Johnson, Adam;Tumpey, Terrence M.
开发流感候选疫苗病毒（CVV）用于大流行前疫苗生产是大流行防备的关键一步。禽或猪源流感病毒的多种亚型和进化枝在任何时候都在世界范围内流行，这使得CVV的连续产生成为必要，以便在新型人畜共患病病毒跨越物种屏障并引起大流行时提供先进的起点。此外，引起人畜共患感染的新型流感病毒的进化和多样性需要持续监测和监视，并且当确定循环病毒和可用CVV之间缺乏抗原匹配时，需要产生新的CVV。世卫组织全球流感计划制定的大流行指南管理反向遗传衍生CVV的设计和制备，这些CVV在人类使用之前必须经过许多安全性和质量测试。确认雪貂中的CVV相对于野生型病毒的毒力减弱是这些关键步骤之一，但关于WHO推荐的针对具有大流行潜力的新型病毒开发的CVV所实现的相对减毒程度的信息很少。为了更好地理解雪貂模型中CVV减毒的程度，我们在雪貂中检测了6种基于A/波多黎各/8/1934的CVV（包括5种不同的甲型流感亚型（H2 N3、H5 N1、H5 N2、H5 N8和H7 N9））与相应野生型病毒的相对毒力。尽管野生型病毒在雪貂中的毒力各不相同，但检查的所有CVV均显示上呼吸道组织中的发病率和病毒脱落减少。此外，与野生型对应物不同，CVV在感染的急性期没有扩散到肺外组织。虽然病毒减毒的幅度在病毒亚型之间变化，但我们共同显示了在哺乳动物模型中具有A/波多黎各/9/1934骨架的CVV的可靠和可重现的减毒。
The development of influenza candidate vaccine viruses (CVVs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. The multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of CVVs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. Furthermore, the evolution and diversity of novel influenza viruses that cause zoonotic infections requires ongoing monitoring and surveillance, and, when a lack of antigenic match between circulating viruses and available CVVs is identified, the production of new CVVs. Pandemic guidelines developed by the WHO Global Influenza Program govern the design and preparation of reverse genetics-derived CVVs, which must undergo numerous safety and quality tests prior to human use. Confirmation of reassortant CVV attenuation of virulence in ferrets relative to wild-type virus represents one of these critical steps, yet there is a paucity of information available regarding the relative degree of attenuation achieved by WHO-recommended CVVs developed against novel viruses with pandemic potential. To better understand the degree of CVV attenuation in the ferret model, we examined the relative virulence of six A/Puerto Rico/8/1934-based CVVs encompassing five different influenza A subtypes (H2N3, H5N1, H5N2, H5N8, and H7N9) compared with the respective wild-type virus in ferrets. Despite varied virulence of wild-type viruses in the ferret, all CVVs examined showed reductions in morbidity and viral shedding in upper respiratory tract tissues. Furthermore, unlike the wild-type counterparts, none of the CVVs spread to extrapulmonary tissues during the acute phase of infection. While the magnitude of virus attenuation varied between virus subtypes, collectively we show the reliable and reproducible attenuation of CVVs that have the A/Puerto Rico/9/1934 backbone in a mammalian model.