Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 2/20/2009
Publication Date: 7/11/2009
Citation: Min, J., Vogel, L., Lu, B., Swayne, D.E., Jin, H., Kemble, G., Subbarao, K. 2009. A live attenuated cold adapted influenza A H7N7 candidate vaccine virus confers protection against homologous and heterologous H7 viruses in mice and ferrets [abstract]. Abstracts of the 28th Annual Meeting of the American Society for Virology Meeting, July 11-15, 2009, Vancouver, British Columbia, Canada. p. 216-217.
Technical Abstract: Highly pathogenic avian influenza (HPAI) H7 subtype viruses pose a pandemic threat to humans because of their ability to transmit directly from domestic poultry to humans. The recent cases of HPAI H7 virus infection in humans underscore their pandemic potential and a need to develop a vaccine to protect humans in the event of an H7 pandemic. A live attenuated H7N7 candidate vaccine virus bearing a modified hemagglutinin (HA) and a wild-type neuraminidase (NA) gene from a highly pathogenic A/Netherlands/219/03 (NL/03) (H7N7) virus and the six internal protein gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, A/Ann Arbor/6/60 ca (AAca) (H2N2) virus, was generated by reverse genetics. The reassortant H7N7 NL03/AAca candidate vaccine virus required trypsin for efficient growth in vitro as predicted by the removal of the multi-basic amino acid cleavage site in the H7 HA gene and showed temperature sensitivity and cold-adaptation phenotypes specified by the internal protein genes of the AAca vaccine donor virus. The candidate vaccine virus was attenuated in mice and ferrets and was not pathogenic for chickens. The H7N7 candidate vaccine virus was immunogenic in mice following intranasal (i.n.) administration of a single dose of the H7N7 NL03/AAca vaccine virus fully protected mice from lethal challenge with homologous and heterologous H7 viruses from Eurasian and North American lineages. Four weeks after receiving two doses of the H7N7 NL03/AAca vaccine, mice developed neutralizing antibodies in the serum and mice were completely protected from pulmonary replication of homologous and heterologous wild-type H7 challenge viruses. Ferrets were also protected from pulmonary replication of the homologous and heterologous H7 challenge viruses following i.n. administration of a single dose of the H7N7 NL03/AAca vaccine virus. The current preclinical studies indicate that the H7N7 NL03/AAca vaccine candidate is safe, immunogenic, and efficacious against antigenically diverse H7 viruses in mice and ferrets and support the evaluation of this vaccine virus in Phase 1 clinical trials in humans.