title: Toxicological evaluation of live attenuated, cold-adapted H5N1 vaccines in ferrets.
abstract: Live attenuated influenza vaccines (LAIV) have several attributes related to safety, immunogenicity, cross-protection against antigenic drift strains, high yield and needle-free administration that make them attractive candidates for control of pandemic influenza. H5N1 LAIV vaccine candidates are attenuated in ferrets, chickens and mice. These vaccine candidates were further characterized in the ferret model to evaluate their toxicity at doses comparable to seasonal LAIV and at doses up to 100-fold higher. The results demonstrated that H5N1 LAIV, even when administered at high doses, is restricted in replication in the lower respiratory tract of ferrets. However, intranasal administration of 0.5 mL can result in deposition of H5N1 LAIV in the ferret lung, where it induces a pulmonary inflammatory response in the absence of significant local replication of the vaccine virus. Thus, smaller vaccine dose volumes should be considered for evaluation of LAIV in animal models.
authors.affiliation: MedImmune, Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA. jinh@medimmune.com
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: S
authors.initials: S
authors.lastname: Manetz
authors.forename: J
authors.initials: J
authors.lastname: Leininger
authors.forename: C
authors.initials: C
authors.lastname: Luke
authors.forename: K
authors.initials: K
authors.lastname: Subbarao
authors.forename: B
authors.initials: B
authors.lastname: Murphy
authors.forename: G
authors.initials: G
authors.lastname: Kemble
authors.forename: K L
authors.initials: KL
authors.lastname: Coelingh
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D005260:Female; D005289:Ferrets; D007249:Inflammation / Q000473:pathology / Q000821:virology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000633:toxicity; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D012137:Respiratory System / Q000821:virology; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000633:toxicity; D014779:Virus Replication / Q000502:physiology
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated