tetano
Editor, Senior Moderator
Antiviral Res. 2017 Apr 10. pii: S0166-3542(16)30791-4. doi: 10.1016/j.antiviral.2017.03.029. [Epub ahead of print]
[h=1]A recombinant H7N9 influenza vaccine with the H7 hemagglutinin transmembrane domain replaced by the H3 domain induces increased cross-reactive antibodies and improved interclade protection in mice.[/h] Wang Y[SUP]1[/SUP], Wu J[SUP]1[/SUP], Xue C[SUP]1[/SUP], Wu Z[SUP]1[/SUP], Lin Y[SUP]1[/SUP], Wei Y[SUP]1[/SUP], Wei X[SUP]1[/SUP], Qin J[SUP]1[/SUP], Zhang Y[SUP]1[/SUP], Wen Z[SUP]1[/SUP], Chen L[SUP]1[/SUP], Liu GD[SUP]2[/SUP], Cao Y[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A H7N9 virus is the latest emerging pandemic threat, and has rapidly diverged into three clades, demanding a H7N9 virus vaccine with broadened protection against unmatched strains. Hemagglutinin (HA)-based structural design approaches for stabilizing HA proteins have provided excitingly promising results. However, none of the HA-based structural design approaches has been applied to a recombinant replicative influenza virus. Here we report that our HA-based structural design approach is a first in the field to generate a recombinant replicative H7N9 virus (H7N9-53TM) showing broadened protection. The H7N9-53TM contains a replaced H3 HA transmembrane domain (TM) in its HA protein. In mice, the inactivated H7N9-53TM vaccine induced significantly higher HI titers, HA-specific IgG titers, and IFN-γ production than the corresponding H7N9-53WT inactivated virus vaccine containing wild-type HA. More excitingly, mice immunized with the H7N9-53TM showed full protection against homologous (H7N9-53) and interclade (H7N9-MCX) challenges with minimal weight loss, no detectable lung viral loads, and no apparent pulmonary lesions and inflammation, while mice immunized with the H7N9-53WT showed partial protection (only 60% against H7N9-MCX) with severe weight loss, detectable lung viral loads, and severe pulmonary lesions and inflammation. In summary, this study presents a better vaccine candidate (H7N9-53TM) against H7N9 pandemics. Furthermore, our HA-based structural design approach would be conceivably applicable to other subtype influenza viruses, especially the viruses from emerging pandemic and epidemic influenza viruses such as H5N1 and H1N1.
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Cross-protection; H7N9; Hemagglutinin; Influenza A virus; Transmembrane domain; Trimerization
PMID: 28408133 DOI: 10.1016/j.antiviral.2017.03.029
[h=1]A recombinant H7N9 influenza vaccine with the H7 hemagglutinin transmembrane domain replaced by the H3 domain induces increased cross-reactive antibodies and improved interclade protection in mice.[/h] Wang Y[SUP]1[/SUP], Wu J[SUP]1[/SUP], Xue C[SUP]1[/SUP], Wu Z[SUP]1[/SUP], Lin Y[SUP]1[/SUP], Wei Y[SUP]1[/SUP], Wei X[SUP]1[/SUP], Qin J[SUP]1[/SUP], Zhang Y[SUP]1[/SUP], Wen Z[SUP]1[/SUP], Chen L[SUP]1[/SUP], Liu GD[SUP]2[/SUP], Cao Y[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A H7N9 virus is the latest emerging pandemic threat, and has rapidly diverged into three clades, demanding a H7N9 virus vaccine with broadened protection against unmatched strains. Hemagglutinin (HA)-based structural design approaches for stabilizing HA proteins have provided excitingly promising results. However, none of the HA-based structural design approaches has been applied to a recombinant replicative influenza virus. Here we report that our HA-based structural design approach is a first in the field to generate a recombinant replicative H7N9 virus (H7N9-53TM) showing broadened protection. The H7N9-53TM contains a replaced H3 HA transmembrane domain (TM) in its HA protein. In mice, the inactivated H7N9-53TM vaccine induced significantly higher HI titers, HA-specific IgG titers, and IFN-γ production than the corresponding H7N9-53WT inactivated virus vaccine containing wild-type HA. More excitingly, mice immunized with the H7N9-53TM showed full protection against homologous (H7N9-53) and interclade (H7N9-MCX) challenges with minimal weight loss, no detectable lung viral loads, and no apparent pulmonary lesions and inflammation, while mice immunized with the H7N9-53WT showed partial protection (only 60% against H7N9-MCX) with severe weight loss, detectable lung viral loads, and severe pulmonary lesions and inflammation. In summary, this study presents a better vaccine candidate (H7N9-53TM) against H7N9 pandemics. Furthermore, our HA-based structural design approach would be conceivably applicable to other subtype influenza viruses, especially the viruses from emerging pandemic and epidemic influenza viruses such as H5N1 and H1N1.
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Cross-protection; H7N9; Hemagglutinin; Influenza A virus; Transmembrane domain; Trimerization
PMID: 28408133 DOI: 10.1016/j.antiviral.2017.03.029