title: Dose-response assessment for influenza A virus based on data sets of infection with its live attenuated reassortants.
abstract: 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 TCID50 (95% CI = 8.8-35 TCID50). The infectivity of wild-type H1N1 virus remains unknown as the data set pooling was unsuccessful.
authors: 1Department of Food, Life and Environmental Sciences, Yamagata University, Yamagata, Japan. to-ru@tds1.tr.yamagata-u.ac.jp
authors: Toru
authors: T
authors: Watanabe
authors: Timothy A
authors: TA
authors: Bartrand
authors: Tatsuo
authors: T
authors: Omura
authors: Charles N
authors: CN
authors: Haas
mesh_terms: D000328:Adult; D000818:Animals; D002648:Child; D004195:Disease Models, Animal; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000472:pathogenicity; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000008:administration & dosage; D007251:Influenza, Human / Q000209:etiology* / Q000821:virology; D008954:Models, Biological; D015233:Models, Statistical; D009976:Orthomyxoviridae Infections / Q000209:etiology / Q000821:virology; D016865:Reassortant Viruses / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D012306:Risk; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014774:Virulence / Q000235:genetics
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated