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.