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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.
Antiviral Res. 2017 07; 143:97-105.AR

Abstract

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.

Authors+Show Affiliations

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.Firstline Biopharmaceuticals Corporation, 12050 167th PL NE, Redmond, WA 98052, USA.State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address: caoych@mail.sysu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28408133

Citation

Wang, Yang, et al. "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." Antiviral Research, vol. 143, 2017, pp. 97-105.
Wang Y, Wu J, Xue C, et al. 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. Antiviral Res. 2017;143:97-105.
Wang, Y., Wu, J., Xue, C., Wu, Z., Lin, Y., Wei, Y., Wei, X., Qin, J., Zhang, Y., Wen, Z., Chen, L., Liu, G. D., & Cao, Y. (2017). 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. Antiviral Research, 143, 97-105. https://doi.org/10.1016/j.antiviral.2017.03.029
Wang Y, et al. 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. Antiviral Res. 2017;143:97-105. PubMed PMID: 28408133.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Wang,Yang, AU - Wu,Jialing, AU - Xue,Chunyi, AU - Wu,Zhihui, AU - Lin,Ying, AU - Wei,Ying, AU - Wei,Xiaona, AU - Qin,Jianru, AU - Zhang,Yun, AU - Wen,Zhifen, AU - Chen,Li, AU - Liu,George Dacai, AU - Cao,Yongchang, Y1 - 2017/04/10/ PY - 2016/12/16/received PY - 2017/03/20/accepted PY - 2017/4/15/pubmed PY - 2017/12/16/medline PY - 2017/4/15/entrez KW - Cross-protection KW - H7N9 KW - Hemagglutinin KW - Influenza A virus KW - Transmembrane domain KW - Trimerization SP - 97 EP - 105 JF - Antiviral research JO - Antiviral Res VL - 143 N2 - 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. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/28408133/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(16)30791-4 DB - PRIME DP - Unbound Medicine ER -