Abstract
Avian influenza H7N9 viruses continue to pose a great threat to public health, which is evident by their high case-fatality rates. Although H7N9 was first isolated in humans in China in 2013, to date, there is no commercial vaccine available against this particular strain. Our previous studies developed a replication-defective influenza virus through mutation of the hemagglutinin (HA) cleavage site from a trypsin-sensitive to an elastase-sensitive motif. In this study, we report the development of a reassortant mutant influenza virus derived from the human isolate A/British Columbia/01/2015 (H7N9) [BC15 (H7N9)], which is the QVT virus. The HA gene of this virus possesses three mutations at the cleavage site, Lys-Gly-Arg were mutated to Gln-Thr-Val at amino acid (aa) positions 337, 338, and 339, respectively. We report this virus to rely on elastase in vitro, possess unaltered replication abilities when elastase was provided compared to the wild type virus in vitro, and to be non-virulent and replication-defective in mice. In addition, we report this virus to induce significant levels of antibodies and IFN-γ and IL-5 secreting cells, and to protect mice against a lethal challenge of the BC15 (H7N9) virus. This protection is demonstrated through the lack of body weight loss, 100% survival rate, and the prevention of BC15 (H7N9) viral replication as well as the reduction of proinflammatory cytokines induced in the mouse lung associated with the influenza disease. Therefore, these results provide strong evidence for the use of this reassortant mutant H7N9 virus as a replication-defective virus vaccine candidate against H7N9 viruses.
Highlights
Avian influenza H7N9 viruses pose a significant threat to public health due to their recently acquired ability to infect humans and cause serious morbidity with high case-fatality rates (CFR)
Avian influenza H7N9 has resulted in a total of five epidemic waves from 2013 to 2017, with the fifth wave resulting in the emergence of the highly pathogenic avian influenza (HPAI) H7N9 virus [3,4]
We report the development of a reassortant mutant H7N9 virus, QTV, which possesses the six internal genes from A/Puerto Rico/8/1934 (H1N1) [PR8 (H1N1)], and the wild type (WT) neuraminidase (NA)
Summary
Avian influenza H7N9 viruses pose a significant threat to public health due to their recently acquired ability to infect humans and cause serious morbidity with high case-fatality rates (CFR). Avian influenza H7N9 has resulted in a total of five epidemic waves from 2013 to 2017, with the fifth wave resulting in the emergence of the highly pathogenic avian influenza (HPAI) H7N9 virus [3,4]. These epidemic waves resulted in CFR ranging from 33% to 45% for LPAI H7N9 and HPAI H7N9, respectively [3].
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