A critical HA1 neutralizing domain of H5N1 influenza in an optimal conformation induces strong cross-protection.
A critical HA1 neutralizing domain of H5N1 influenza in an optimal conformation induces strong cross-protection.
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DOI：
10.1371/journal.pone.0053568
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jiang S
中科院分区：
文献类型：
--
作者：
Du L;Zhao G;Sun S;Zhang X;Zhou X;Guo Y;Li Y;Zhou Y;Jiang S
The highly pathogenic avian influenza (HPAI) H5N1 viruses, especially the laboratory-generated H5N1 mutants, have demonstrated the potential to cross the species barrier and infect mammals and humans. Consequently, the design of an effective and safe anti-H5N1 vaccine is essential. We previously demonstrated that the full-length hemagglutinin 1 (HA1) could induce significant neutralizing antibody response and protection. Here, we intended to identify the critical neutralizing domain (CND) in an optimal conformation that can elicit strong cross-neutralizing antibodies and protection against divergent H5N1 strains. We thus constructed six recombinant proteins covering different regions of HA1 of A/Anhui/1/2005(H5N1), each of which was fused with foldon (Fd) and Fc of human IgG. We found that the critical fragment fused with Fd/Fc (HA-13–263-Fdc, H5 numbering) that could elicit the strongest neutralizing antibody response is located in the N-terminal region of HA1 (residues 13–263), which covers the receptor-binding domain (RBD, residues 112–263). We then constructed three additional recombinants fused with Fd plus His tag (HA-13–263-Fd-His), Fc only (HA-13–263-Fc), and His tag only (HA-13–263-His), respectively. We found that the HA-13–263-Fdc, which formed an oligomeric conformation, induced the strongest neutralizing antibody response and cross-protection against challenges of two tested H5N1 virus strains covering clade 1: A/VietNam/1194/2004 (VN/1194) or clade 2.3.4: A/Shenzhen/406H/06 (SZ/406H), while HA-13–263-Fc dimer and HA-13–263-Fd-His trimer elicited higher neutralizing antibody response and protection than HA-13–263-His monomer. These results suggest that the oligomeric form of the CND containing the RBD can be further developed as an effective and safe vaccine for cross-protection against divergent strains of H5N1 viruses.
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影响因子：
64.8
作者：
Fouchier R;Osterhaus AB;Steinbruner J;Yuen KY;Henderson DA;Klotz L;Sylvester E;Taubenberger JK;Ebright RH;Heymann DL
通讯作者：
Heymann DL
影响因子：
5.4
作者：
Bodewes, R.;Kreijtz, J. H. C. M.;Rimmelzwaan, G. F.
通讯作者：
Rimmelzwaan, G. F.
影响因子：
15.8
作者：
Khurana S;Suguitan AL Jr;Rivera Y;Simmons CP;Lanzavecchia A;Sallusto F;Manischewitz J;King LR;Subbarao K;Golding H
通讯作者：
Golding H
影响因子：
5.5
作者：
Khurana, Surender;Larkin, Christopher;Golding, Hana
通讯作者：
Golding, Hana
影响因子：
5.4
作者：
Khurana, Surender;Wu, Jian;Golding, Hana
通讯作者：
Golding, Hana