Influenza Viruses with Rearranged Genomes as Live-Attenuated Vaccines | Zendy

Lindomar Pena | Zendy; Troy C. Sutton | Zendy; Ashok Chockalingam | Zendy; Sachin Kumar | Zendy; Matthew Angel | Zendy; Hongxia Shao | Zendy; Hongjun Chen | Zendy; Weizhong Li | Zendy; Daniel R. Pérez | Zendy

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Influenza Viruses with Rearranged Genomes as Live-Attenuated Vaccines

Author(s) -

Lindomar Pena,

Troy C. Sutton,

Ashok Chockalingam,

Sachin Kumar,

Matthew Angel,

Hongxia Shao,

Hongjun Chen,

Weizhong Li,

Daniel R. Pérez

Publication year - 2013

Publication title -

journal of virology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.617

H-Index - 292

eISSN - 1070-6321

pISSN - 0022-538X

DOI - 10.1128/jvi.02490-12

Subject(s) - virology , biology , influenza a virus subtype h5n1 , reassortment , hemagglutinin (influenza) , virus , live attenuated influenza vaccine , attenuated vaccine , influenza a virus , h5n1 genetic structure , pandemic , orthomyxoviridae , genome , viral replication , gene , influenza vaccine , genetics , infectious disease (medical specialty) , virulence , medicine , covid-19 , disease , pathology

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.

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