[Source: Journal of Virology, full text: (LINK). Abstract, edited.]
Influenza viruses with rearranged genomes as live-attenuated vaccines
Lindomar Pena, Troy Sutton, Ashok Chockalingam, Sachin Kumar, Matthew Angel, Hongxia Shao, Hongjun Chen, Weizhong Li and Daniel R. Perez*
Author Affiliations: Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, U.S.
H5N1 and H9N2 avian influenza 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 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 HA open reading frame (ORF) from the segment 8 vRNA. These vectors had reduced polymerase activity 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 genome has great potential for the development of improved vaccines against influenza as well as other pathogens.
* Corresponding author: Daniel R. Perez. E-mail: email@example.com
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