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Dose-Response Assessment for Influenza A Virus Based on Data Sets of Infection with its Live Attenuated Reassortants

机译：基于感染数据集及其活体减毒重组子的甲型流感病毒剂量反应评估

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Reported data sets on infection of volunteers challenged with wild-type influenza A virus at graded doses are few. Alternatively, we aimed at developing a dose-response assessment for this virus based on the data sets for its live attenuated reassortants. Eleven data sets for live attenuated reassortants that were fit to beta-Poisson and exponential dose-response models. Dose-response relationships for those reassortants were characterized by pooling analysis of the data sets with respect to virus subtype (H1N1 or H3N2), attenuation method (cold-adapted or avian-human gene reassortment), and human age (adults or children). Furthermore, by comparing the above data sets to a limited number of reported data sets for wild-type virus, we quantified the degree of attenuation of wild-type virus with gene reassortment and estimated its infectivity. As a result, dose-response relationships of all reassortants were best described by a beta-Poisson model. Virus subtype and human age were significant factors determining the dose-response relationship, whereas attenuation method affected only the relationship of H1N1 virus infection to adults. The data sets for H3N2 wild-type virus could be pooled with those for its reassortants on the assumption that the gene reassortment attenuates wild-type virus by at least 63 times and most likely 1,070 times. Considering this most likely degree of attenuation, 10% infectious dose of H3N2 wild-type virus for adults was estimated at 18 TCID_(50) (95% CI = 8.8-35 TCID_(50)). The infectivity of wild-type H1N1 virus remains unknown as the data set pooling was unsuccessful.
机译：关于以分级剂量感染野生型A型流感病毒的志愿者感染的报道数据很少。或者，我们旨在根据该病毒减毒活重组子的数据集，对该病毒进行剂量反应评估。适用于β-泊松和指数剂量反应模型的11个减毒活重组体数据集。通过对病毒亚型（H1N1或H3N2），减毒方法（冷适应或禽-人基因重配）和人类年龄（成人或儿童）的数据集进行汇总分析，确定了这些重配物的剂量反应关系。此外，通过将上述数据集与有限数量的野生型病毒报道数据集进行比较，我们通过基因重排量化了野生型病毒的减毒程度，并评估了其传染性。结果，用β-泊松模型可以最好地描述所有重配物的剂量反应关系。病毒亚型和人的年龄是决定剂量反应关系的重要因素，而减毒方法仅影响H1N1病毒感染与成年人之间的关系。 H3N2野生型病毒的数据集可以与其重配子的数据集合并，其前提是基因重配能使野生型病毒减少至少63倍，最有可能是1,070倍。考虑到这种最可能的衰减程度，估计成人的H3N2野生型病毒的10％感染剂量为18 TCID_（50）（95％CI = 8.8-35 TCID_（50））。由于数据集汇总失败，野生型H1N1病毒的传染性仍然未知。

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