title: Influenza viruses with rearranged genomes as live-attenuated vaccines.
abstract: H5N1 and H9N2 avian influenza virus subtypes top the World Health Organization's list for the greatest pandemic potential. Inactivated H5N1 vaccines induce limited immune responses and, in the case of live-attenuated influenza virus vaccines (LAIV), there are safety concerns regarding the possibility of reassortment between the H5 gene segment and circulating influenza viruses. In order to overcome these drawbacks, we rearranged the genome of an avian H9N2 influenza virus and expressed the entire H5 hemagglutinin open reading frame (ORF) from the segment 8 viral RNA. These vectors had reduced polymerase activities as well as viral replication in vitro and excellent safety profiles in vivo. Immunization with the dual H9-H5 influenza virus resulted in protection against lethal H5N1 challenge in mice and ferrets, and also against a potentially pandemic H9 virus. Our studies demonstrate that rearranging the influenza virus genome has great potential for the development of improved vaccines against influenza virus as well as other pathogens.
authors: Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA.
authors: Lindomar
authors: L
authors: Pena
authors: Troy
authors: T
authors: Sutton
authors: Ashok
authors: A
authors: Chockalingam
authors: Sachin
authors: S
authors: Kumar
authors: Matthew
authors: M
authors: Angel
authors: Hongxia
authors: H
authors: Shao
authors: Hongjun
authors: H
authors: Chen
authors: Weizhong
authors: W
authors: Li
authors: Daniel R
authors: DR
authors: Perez
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002645:Chickens; D005260:Female; D005289:Ferrets; D005818:Genetic Engineering; D016679:Genome, Viral; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated