Inclusion of membrane-anchored LTB or flagellin protein in H5N1 virus-like particles enhances protective responses following intramuscular and oral immunization of mice

文献类型： 外文期刊

第一作者： Ren, Zhiguang

作者： Ren, Zhiguang;Yang, Zhengyan;Wang, Zhizeng;Ren, Zhiguang;Zhao, Yongkun;Liu, Jing;Ji, Xianliang;Meng, Lingnan;Wang, Tiecheng;Sun, Weiyang;Zhang, Kun;Sang, Xiaoyu;Yu, Zhijun;Li, Yuanguo;Feng, Na;Wang, Hualei;Yang, Songtao;Gao, Yuwei;Xia, Xianzhu;Ren, Zhiguang;Yang, Zhengyan;Wang, Zhizeng;Gao, Yuwei;Xia, Xianzhu;Gao, Yuwei;Xia, Xianzhu;Liu, Jing;Liu, Jing

作者机构：

关键词： H5N1 influenza; Chimeric VLPs; Vaccine; Oral immunization; Mucosally vaccinated; Immunogenicity

期刊名称：VACCINE （ 影响因子：3.641； 五年影响因子：3.816 ）

ISSN： 0264-410X

年卷期： 2018 年 36 卷 40 期

页码：

收录情况： SCI

摘要： We previously demonstrated that intramuscular immunization with virus-like particles (VLPs) composed of the haemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of AimeerkatiShanghai/SH1/2012 (Glade 2.3.2.1) protected mice from lethal challenge with viruses from other H5 HPAI clades. The inclusion of additional proteins that can serve as immunological adjuvants in VLPs may enhance adaptive immune responses following vaccination, and oral vaccines may represent the safest choice. Here, we report the generation of H5N1 VLPs composed of the viral HA, NA, and M1 proteins and membrane-anchored forms of the Escherichia coli heat-labile enterotoxin B subunit protein (LTB) or the Toll-like receptor 5 ligand flagellin (Flic). Mice intramuscularly or orally immunized with VLPs containing LTB or Flic generated greater humoural and cellular immune responses than those administered H5N1 VLPs without LTB or Flic. Intramuscular immunization with VLPs protected mice from lethal challenge with homologous or heterologous H5N1 viruses irrespective of whether the VLPs additionally included LTB or Flic. In contrast, oral immunization of mice with LTB- or Flic-VLPs conferred substantial protection against lethal challenge with both homologous and heterologous H5N1 influenza viruses, whereas mice immunized orally with VLPs lacking LTB and Flic universally succumbed to infection. Mice immunized orally with LTB- or Flic-VLPs showed 10-fold higher virus-specific IgG titres than mice immunized with H5N1-VLPs lacking LTB or Flic. Collectively, these results indicate that the inclusion of immunostimulatory proteins, such as LTB and Flic, in VLP-based vaccines may represent a promising new approach for the control of current H5N1 HPAI outbreaks by eliciting higher humoural and cellular immune responses and conferring improved cross-Glade protection. (C) 2018 Elsevier Ltd. All rights reserved.

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