Influenza H7N9 LAH-HBc virus-like particle vaccine with adjuvant protects mice against homologous and heterologous influenza viruses

被引:24
作者
Zheng, Dan [1 ]
Chen, Shaoheng [1 ]
Qu, Di [2 ]
Chen, Jianjun [3 ]
Wang, Fuyan [4 ]
Zhang, Ran [5 ]
Chen, Ze [1 ,5 ]
机构
[1] Shanghai Inst Biol Prod, Shanghai 200052, Peoples R China
[2] Fudan Univ, Biosafety Level Lab 3, Shanghai 200032, Peoples R China
[3] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
[4] Cent S Univ, Xiangya Sch Med, Dept Immunol, Changsha 410078, Hunan, Peoples R China
[5] Hunan Normal Univ, Coll Med, Changsha 410013, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
Influenza; H7N9; LAH-HBc VLP; Adjuvant; IMMUNOGLOBULIN-A; INTRACELLULAR NEUTRALIZATION; CROSS-PROTECTION; INDUCTION; INFECTION; IMMUNITY;
D O I
10.1016/j.vaccine.2016.11.026
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The long alpha-helix (LAH) region located in influenza virus hemagglutinin (HA) shows conservation among different influenza A strains, which could be used as a candidate target of influenza vaccines. Moreover, the hepatitis B virus core protein (HBc) is a carrier for heterologous epitopes in eliciting effective immune responses. We inserted the LAH region of H7N9 influenza virus into the HBc and prepared the LAH-HBc protein, which were capable of self-assembly into virus-like particles (VLP), by using E. coli expression system. Intranasal immunization of the LAH-HBc VLP in combination with chitosan adjuvant or CTB* adjuvant in mice could induce both humoral and cellular immune responses effectively and provide complete protection against lethal challenge of homologous H7N9 virus or heterologous H3N2 virus, as well as partial protection against lethal challenge of heterologous H1N1 virus. These results provide a proof of concept for LAH-HBc VLP vaccine that would be fast and easy to be produced and might be an ideal candidate as a rapid-response tool against a future influenza pandemic. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6464 / 6471
页数:8
相关论文
共 36 条
[11]   Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus [J].
Gao, Rongbao ;
Cao, Bin ;
Hu, Yunwen ;
Feng, Zijian ;
Wang, Dayan ;
Hu, Wanfu ;
Chen, Jian ;
Jie, Zhijun ;
Qiu, Haibo ;
Xu, Ke ;
Xu, Xuewei ;
Lu, Hongzhou ;
Zhu, Wenfei ;
Gao, Zhancheng ;
Xiang, Nijuan ;
Shen, Yinzhong ;
He, Zebao ;
Gu, Yong ;
Zhang, Zhiyong ;
Yang, Yi ;
Zhao, Xiang ;
Zhou, Lei ;
Li, Xiaodan ;
Zou, Shumei ;
Zhang, Ye ;
Li, Xiyan ;
Yang, Lei ;
Guo, Junfeng ;
Dong, Jie ;
Li, Qun ;
Dong, Libo ;
Zhu, Yun ;
Bai, Tian ;
Wang, Shiwen ;
Hao, Pei ;
Yang, Weizhong ;
Zhang, Yanping ;
Han, Jun ;
Yu, Hongjie ;
Li, Dexin ;
Gao, George F. ;
Wu, Guizhen ;
Wang, Yu ;
Yuan, Zhenghong ;
Shu, Yuelong .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (20) :1888-1897
[12]   Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host [J].
Gao, Yuwei ;
Zhang, Ying ;
Shinya, Kyoko ;
Deng, Guohua ;
Jiang, Yongping ;
Li, Zejun ;
Guan, Yuntao ;
Tian, Guobin ;
Li, Yanbing ;
Shi, Jianzhong ;
Liu, Liling ;
Zeng, Xianying ;
Bu, Zhigao ;
Xia, Xianzhu ;
Kawaoka, Yoshihiro ;
Chen, Hualan .
PLOS PATHOGENS, 2009, 5 (12)
[13]   Prospects of HA-Based Universal Influenza Vaccine [J].
Hashem, Anwar M. .
BIOMED RESEARCH INTERNATIONAL, 2015, 2015
[14]   COMPARISON OF INTRANASAL INOCULATION OF INFLUENZA HA VACCINE COMBINED WITH CHOLERA TOXIN-B SUBUNIT WITH ORAL OR PARENTERAL VACCINATION [J].
HIRABAYASHI, Y ;
KURATA, H ;
FUNATO, H ;
NAGAMINE, T ;
AIZAWA, C ;
TAMURA, S ;
SHIMADA, K ;
KURATA, T .
VACCINE, 1990, 8 (03) :243-248
[15]   A RECOMBINANT SALMONELLA-TYPHIMURIUM VACCINE INDUCES LOCAL IMMUNITY BY 4 DIFFERENT ROUTES OF IMMUNIZATION [J].
HOPKINS, S ;
KRAEHENBUHL, JP ;
SCHODEL, F ;
POTTS, A ;
PETERSON, D ;
DEGRANDI, P ;
NARDELLIHAEFLIGER, D .
INFECTION AND IMMUNITY, 1995, 63 (09) :3279-3286
[16]   Influenza Vaccines: Challenges and Solutions [J].
Houser, Katherine ;
Subbarao, Kanta .
CELL HOST & MICROBE, 2015, 17 (03) :295-300
[17]   H3 Stalk-Based Chimeric Hemagglutinin Influenza Virus Constructs Protect Mice from H7N9 Challenge [J].
Krammer, Florian ;
Margine, Irina ;
Hai, Rong ;
Flood, Alexander ;
Hirsh, Ariana ;
Tsvetnitsky, Vadim ;
Chen, Dexiang ;
Palese, Peter .
JOURNAL OF VIROLOGY, 2014, 88 (04) :2340-2343
[18]   Influenza virus hemagglutinin stalk-based antibodies and vaccines [J].
Krammer, Florian ;
Palese, Peter .
CURRENT OPINION IN VIROLOGY, 2013, 3 (05) :521-530
[19]   Human H7N9 avian influenza virus infection: a review and pandemic risk assessment [J].
Lai, Kang Yiu ;
Ng, George Wing Yiu ;
Wong, Kit Fai ;
Hung, Ivan Fan Ngai ;
Hong, Jeffrey Kam Fai ;
Cheng, Fanny Fan ;
Chan, John Kwok Cheung .
EMERGING MICROBES & INFECTIONS, 2013, 2
[20]   Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China [J].
Li, Qun ;
Zhou, Lei ;
Zhou, Minghao ;
Chen, Zhiping ;
Li, Furong ;
Wu, Huanyu ;
Xiang, Nijuan ;
Chen, Enfu ;
Tang, Fenyang ;
Wang, Dayan ;
Meng, Ling ;
Hong, Zhiheng ;
Tu, Wenxiao ;
Cao, Yang ;
Li, Leilei ;
Ding, Fan ;
Liu, Bo ;
Wang, Mei ;
Xie, Rongheng ;
Gao, Rongbao ;
Li, Xiaodan ;
Bai, Tian ;
Zou, Shumei ;
He, Jun ;
Hu, Jiayu ;
Xu, Yangting ;
Chai, Chengliang ;
Wang, Shiwen ;
Gao, Yongjun ;
Jin, Lianmei ;
Zhang, Yanping ;
Luo, Huiming ;
Yu, Hongjie ;
He, Jianfeng ;
Li, Qi ;
Wang, Xianjun ;
Gao, Lidong ;
Pang, Xinghuo ;
Liu, Guohua ;
Yan, Yansheng ;
Yuan, Hui ;
Shu, Yuelong ;
Yang, Weizhong ;
Wang, Yu ;
Wu, Fan ;
Uyeki, Timothy M. ;
Feng, Zijian .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (06) :520-532