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 candidat...

Full description

Saved in:
Bibliographic Details
Published in:Vaccine 2007-12, Vol.25 (52), p.8664-8672
Main Authors: Jin, H, Manetz, S, Leininger, J, Luke, C, Subbarao, K, Murphy, B, Kemble, G, Coelingh, K.L
Format: Article
Language:English
Subjects:
Administration, Intranasal
Allergy and Immunology
Animal models
Animals
Antigens
Applied microbiology
Biological and medical sciences
Candidates
Female
Ferrets
Fundamental and applied biological sciences. Psychology
Genetic engineering
H5N1
Immunogenicity
Inflammation - pathology
Inflammation - virology
Influenza
Influenza A Virus, H5N1 Subtype - immunology
Influenza Vaccines - administration & dosage
Influenza Vaccines - adverse effects
Influenza Vaccines - toxicity
Lung - pathology
Lung - virology
Lungs
Male
Microbiology
Mustela
Pandemics
Plasmids
Respiratory System - virology
Respiratory tract
Toxicology
Vaccine
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, Attenuated - adverse effects
Vaccines, Attenuated - toxicity
Virus Replication - physiology
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2007.10.032