tetano
Editor, Senior Moderator
Virus Res. 2017 Sep 11. pii: S0168-1702(17)30099-0. doi: 10.1016/j.virusres.2017.09.008. [Epub ahead of print]
[h=1]Recombinant influenza H7 hemagglutinin containing CFLLC minidomain in the transmembrane domain showed enhanced cross-protection in mice.[/h] Wang Y[SUP]1[/SUP], Zhang Y[SUP]1[/SUP], Wu J[SUP]1[/SUP], Lin Y[SUP]1[/SUP], Wu Z[SUP]1[/SUP], Wei Y[SUP]1[/SUP], Wei X[SUP]1[/SUP], Qin J[SUP]1[/SUP], Xue C[SUP]1[/SUP], Liu GD[SUP]2[/SUP], Cao Y[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Since February 2013, H7N9 influenza virus, causing human infections with high mortality in China, has been a potential pandemic threat. The H7N9 viruses are found to diverge into distinct genotypes as other influenza viruses; thus a vaccine that can provide sufficient cross-protection against different genotypes of H7N9 viruses is urgently needed. Our previous studies demonstrated that the HA-based structural design approach by introducing a CFLLC minidomain into transmembrane domain (TM) of H1, H5 or H9 hemagglutinin (HA) proteins by replacing with H3 subtype HA TM could enhance their cross-protection. In this study, we used Sf9 insect cell expression system to express recombinant H7 HA proteins H7-53WT, in which HA gene was derived from H7N9-53 strain, and H7-53TM containing CFLLC minidomian by replacing its TM domain with H3 HA TM. We investigated whether introduction of CFLLC minidomain into H7 HA (H7-53TM) could increase its cross-reactivity and cross-protection against different genotypes of H7N9 viruses. The results showed that the H7-53TM either with or without squalene adjuvant induced increased HI antibodies, serum IgG antibodies, and IFN-γ production to a panel of 7 H7N9 viruses in mice. Vaccinated animals with H7-53TM alone showed complete protection against challenge with heterologous H7N9-MCX strain, while H7-53WT alone showed incomplete protection (80%). Furthermore, mice vaccinated with H7-53TM HA showed less body weight loss and less pulmonary lesions and inflammation after challenge with homologous or heterologous H7N9 viruses, comparing to H7-53WT. In summary, this study presents a better subunit vaccine candidate (H7-53TM) against potential H7N9 pandemic.
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Cross-protection; H7N9; Hemagglutinin; Influenza A virus; Transmembrane domain; Trimerization
PMID: 28912070 DOI: 10.1016/j.virusres.2017.09.008
[h=1]Recombinant influenza H7 hemagglutinin containing CFLLC minidomain in the transmembrane domain showed enhanced cross-protection in mice.[/h] Wang Y[SUP]1[/SUP], Zhang Y[SUP]1[/SUP], Wu J[SUP]1[/SUP], Lin Y[SUP]1[/SUP], Wu Z[SUP]1[/SUP], Wei Y[SUP]1[/SUP], Wei X[SUP]1[/SUP], Qin J[SUP]1[/SUP], Xue C[SUP]1[/SUP], Liu GD[SUP]2[/SUP], Cao Y[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Since February 2013, H7N9 influenza virus, causing human infections with high mortality in China, has been a potential pandemic threat. The H7N9 viruses are found to diverge into distinct genotypes as other influenza viruses; thus a vaccine that can provide sufficient cross-protection against different genotypes of H7N9 viruses is urgently needed. Our previous studies demonstrated that the HA-based structural design approach by introducing a CFLLC minidomain into transmembrane domain (TM) of H1, H5 or H9 hemagglutinin (HA) proteins by replacing with H3 subtype HA TM could enhance their cross-protection. In this study, we used Sf9 insect cell expression system to express recombinant H7 HA proteins H7-53WT, in which HA gene was derived from H7N9-53 strain, and H7-53TM containing CFLLC minidomian by replacing its TM domain with H3 HA TM. We investigated whether introduction of CFLLC minidomain into H7 HA (H7-53TM) could increase its cross-reactivity and cross-protection against different genotypes of H7N9 viruses. The results showed that the H7-53TM either with or without squalene adjuvant induced increased HI antibodies, serum IgG antibodies, and IFN-γ production to a panel of 7 H7N9 viruses in mice. Vaccinated animals with H7-53TM alone showed complete protection against challenge with heterologous H7N9-MCX strain, while H7-53WT alone showed incomplete protection (80%). Furthermore, mice vaccinated with H7-53TM HA showed less body weight loss and less pulmonary lesions and inflammation after challenge with homologous or heterologous H7N9 viruses, comparing to H7-53WT. In summary, this study presents a better subunit vaccine candidate (H7-53TM) against potential H7N9 pandemic.
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Cross-protection; H7N9; Hemagglutinin; Influenza A virus; Transmembrane domain; Trimerization
PMID: 28912070 DOI: 10.1016/j.virusres.2017.09.008