Please wait a minute...
Journal of Integrative Agriculture  2022, Vol. 21 Issue (7): 2086-2094    DOI: 10.1016/S2095-3119(22)63904-2
Animal Science · Veterinary Medicine Advanced Online Publication | Current Issue | Archive | Adv Search |
Protective efficacy of an H5/H7 trivalent inactivated vaccine (H5-Re13, H5-Re14, and H7-Re4 strains) in chickens, ducks, and geese against newly detected H5N1, H5N6, H5N8, and H7N9 viruses

ZENG Xian-ying*, HE Xin-wen*, MENG Fei, MA Qi, WANG Yan, BAO Hong-mei, LIU Yan-jing, DENG Guo-hua, SHI Jian-zhong, LI Yan-bing, TIAN Guo-bin, CHEN Hua-lan

State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, P.R.China

Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
摘要  

本研究通过抗原性分析发现,2020年至2021年在野鸟或家禽中分离的一些H5N6、H5N8和H5N1病毒与我国大规模应用的H5疫苗种毒株(H5-Re11株和H5-Re12株)的抗原性存在较大差异,部分2021年分离的H7N9病毒也与我国使用的H7-Re3株疫苗毒株存在抗原性差异。为保持疫苗株与监测毒株之间良好的抗原匹配性,本研究利用反向遗传学操作技术,构建出针对抗原变异毒株的3株重组疫苗种毒(H5-Re13、H5-Re14和H7-Re4),用于疫苗的更新。其中,H5-Re13疫苗株的HA和NA基因来自于2.3.4.4h分支的H5N6病毒(DK/FJ/S1424/20),H5-Re14疫苗株的HA和NA基因来自于2.3.4.4b分支的H5N8病毒(WS/SX/4-1/20),H7-Re4疫苗株的HA和NA基因来自于2021年分离的H7N9病毒(CK/YN/SD024/21)。进一步使用上述3株重组病毒制备新型H5+H7三价灭活疫苗,进行鸡、鸭和鹅的免疫效力研究。结果显示,H5+H7三价灭活疫苗接种鸡、鸭和鹅后均可诱导出良好的HI抗体反应;SPF鸡接种疫苗后3周时,用2020年和2021年分离到的5株不同H5和H7病毒攻击,包括3株2.3.4.4b分支病毒(H5N1、H5N6和H5N8病毒各1株)、1株2.3.4.4h分支的H5N6病毒和1株H7N9病毒,攻毒后所有对照组鸡均出现高滴度的排毒,并在攻毒后4天内全部死亡,而疫苗接种组鸡则完全抵御病毒的感染;接种疫苗的鸭和鹅在攻击2.3.4.4h或2.3.4.4b分支H5病毒后也获得完全免疫保护。本研究结果表明,新型H5+H7三价疫苗具有良好的免疫原性,对于近期监测到的H5N1、H5N6、H5N8和H7N9病毒的攻击可提供完全的免疫保护作用。鉴于不同H5病毒和H7N9病毒对家禽的威胁,本研究建议我国广泛使用该H5+H7三价灭活疫苗,并推荐该疫苗在其他受到H5和H7病毒威胁的国家应用。




Abstract  

Some H5 viruses isolated in poultry or wild birds between 2020 and 2021 were found to be antigenically different from the vaccine strains (H5-Re11 and H5-Re12) used in China.  In this study, we generated three new recombinant vaccine seed viruses by using reverse genetics and used them for vaccine production.  The vaccine strain H5-Re13 contains the hemagglutinin (HA) and neuraminidase (NA) genes of an H5N6 virus that bears the clade 2.3.4.4h HA gene, H5-Re14 contains the HA and NA genes of an H5N8 virus that bears the clade 2.3.4.4b HA gene, and H7-Re4 contains the HA and NA genes of H7N9 virus detected in 2021.  We evaluated the protective efficacy of the novel H5/H7 trivalent inactivated vaccine in chickens, ducks, and geese.  The inactivated vaccine was immunogenic and induced substantial antibody responses in the birds tested.  Three weeks after vaccination, chickens were challenged with five different viruses detected in 2020 and 2021: three viruses (an H5N1 virus, an H5N6 virus, and an H5N8 virus) bearing the clade 2.3.4.4b HA gene, an H5N6 virus bearing the clade 2.3.4.4h HA gene, and an H7N9 virus.  All of the control birds shed high titers of virus and died within 4 days post-challenge, whereas the vaccinated chickens were completely protected from these viruses.  Similar protective efficacy against H5 viruses bearing the clade 2.3.4.4h or 2.3.4.4b HA gene was observed in ducks and geese.  Our study indicates that the newly updated H5/H7 vaccine can provide solid protection against the H5 and H7N9 viruses that are currently circulating in nature.  

Keywords:  avian influenza        H5/H7 trivalent vaccine       H5-Re13       H5-Re14       H7-Re4 strains       protective efficacy       chickens       ducks and geese  
Received: 14 April 2022   Accepted: 23 April 2022
Fund: 

This work was supported by the National Key Research and Development Program of China (2021YFD1800200), the Laboratory for Lingnan Modern Agriculture Project (NT2021007), and the China Agriculture Research System of the MOF and MARA (CARS-41-G12).


About author:  ZENG Xian-ying, E-mail: zengxianying@caas.cn; Correspondence CHEN Hua-lan, Tel: +86-451-51997168, Fax: +86-451-51997166, E-mail: chenhualan@caas.cn; TIAN Guo-bin, Tel: +86-451-51051681, Fax: +86-451-51997166, E-mail: tianguobin@caas.cn * These authors contributed equally to this study *These authors contributed equally to this study.

Cite this article: 

ZENG Xian-ying, HE Xin-wen, MENG Fei, MA Qi, WANG Yan, BAO Hong-mei, LIU Yan-jing, DENG Guo-hua, SHI Jian-zhong, LI Yan-bing, TIAN Guo-bin, CHEN Hua-lan. 2022. Protective efficacy of an H5/H7 trivalent inactivated vaccine (H5-Re13, H5-Re14, and H7-Re4 strains) in chickens, ducks, and geese against newly detected H5N1, H5N6, H5N8, and H7N9 viruses. Journal of Integrative Agriculture, 21(7): 2086-2094.

Alexander D J, Brown I H. 2009. History of highly pathogenic avian influenza. Revue Scientifique et Technique-Office International Des Epizooties, 28, 19–38.
Baek Y G, Lee Y N, Lee D H, Shin J I, Lee J H, Chung D H, Lee E K, Heo G B, Sagong M, Kye S J, Lee K N, Lee M H , Lee Y J. 2021. Multiple reassortants of H5N8 Clade 2.3.4.4b highly pathogenic avian influenza viruses detected in South Korea during the winter of 2020–2021. Viruses, 13, 490.
Bevins S N, Shriner S A, Cumbee Jr J C, Dilione K E, Douglass K E, Ellis J W, Killian M L, Torchetti M K, Lenoch J B. 2022. Intercontinental movement of highly pathogenic avian Influenza A(H5N1) clade 2.3.4.4 virus to the United States, 2021. Emerging Microbes & Infections, 28, doi: 10.3201/eid2805.220318.
Chen H. 2009. H5N1 avian influenza in China. Science China (Life Sciences), 52, 419–427.
Chen H, Deng G, Li Z, Tian G, Li Y, Jiao P, Zhang L, Liu Z, Webster R G, Yu K. 2004. The evolution of H5N1 influenza viruses in ducks in southern China. Proceedings of the National Academy of Sciences of the United States of America, 101, 10452–10457.
Cui P, Zeng X, Li X, Li Y, Shi J, Zhao C, Qu Z, Wang Y, Guo J, Gu W, Ma Q, Zhang Y, Lin W, Li M, Tian J, Wang D, Xing X, Liu Y, Pan S, Zhang Y, et al. 2022. Genetic and biological characteristics of the globally circulating H5N8 avian influenza viruses and the protective efficacy offered by the poultry vaccine currently used in China. Science China (Life Sciences), 65, 795–808. 
Cui Y, Li Y, Li M, Zhao L, Wang D, Tian J, Bai X, Ci Y, Wu S, Wang F, Chen X, Ma S, Qu Z, Yang C, Liu L, Shi J, Guan Y, Zeng X, Tian G, Cui P, et al. 2020. Evolution and extensive reassortment of H5 influenza viruses isolated from wild birds in China over the past decade. Emerging Infectious Diseases, 9, 1793–1803.
Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, et al. 2013. Human infection with a novel avian-origin influenza A (H7N9) virus. The New England Journal of Medicine, 368, 1888–1897.
Gu W, Shi J, Cui P, Yan C, Zhang Y, Wang C, Zhang Y, Xing X, Zeng X, Liu L, Tian G, Suzuki Y, Li C, Deng G, Chen H. 2022. Novel H5N6 reassortants bearing the clade 2.3.4.4b HA gene of H5N8 virus have been detected in poultry and caused multiple human infections in China. Emerging Microbes & Infections, 11, 1–27. 
Hui D S C, Lee N, Chan P K S. 2017. Avian influenza A (H7N9) virus infections in humans across five epidemics in mainland China, 2013–2017. Journal of Thoracic Disease, 9, 4808–4811.
Lewis N S, Banyard A C, Whittard E, Karibayev T, Al Kafagi T, Chvala I, Byrne A, Meruyert Akberovna S, King J, Harder T, Grund C, Essen S, Reid S M, Brouwer A, Zinyakov N G, Tegzhanov A, Irza V, Pohlmann A, Beer M, et al. 2021. Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020. Emerging Microbes & Infections, 10, 148–151. 
Li C, Bu Z, Chen H. 2014. Avian influenza vaccines against H5N1 ‘bird flu’. Trends in Biotechnology, 32, 147–156.
Li Y, Li M, Li Y, Tian J, Bai X, Yang C, Shi J, Ai R, Chen W, Zhang W, Li J, Kong Y, Guan Y, Chen H. 2020. Outbreaks of highly pathogenic avian influenza (H5N6) Virus Subclade 2.3.4.4h in Swans, Xinjiang, Western China, 2020. Emerging Infectious Diseases, 26, 2956–2960. 
Li Y, Liu L, Zhang Y, Duan Z, Tian G, Zeng X, Shi J, Zhang L, Chen H. 2011. New avian influenza virus (H5N1) in wild birds, Qinghai, China. Emerging Infectious Diseases, 17, 265–267.
Li Y, Shi J, Zhong G, Deng G, Tian G, Ge J, Zeng X, Song J, Zhao D, Liu L, Jiang Y, Guan Y, Bu Z, Chen H. 2010. Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry, and humans in China from 2004 to 2009. Journal of Virology, 84, 8389–8397. 
MARA (Ministry of Agriculture and Rural Affairs of China). 2020. Bulletin no.314 (in Chinese). http://www.moa.gov.cn/govpublic/xmsyj/202007/t20200721_6348991.htm
Moncla L. 2022. Real-time tracking of influenza A/H5NX virus evolution. Nextstrain/avian-flu. [2022-3-10]. https://nextstrain.org/flu/avian/h5nx/ha
Rijks J M, Hesselink H, Lollinga P, Wesselman R, Prins P, Weesendorp E, Engelsma M, Heutink R, Harders F, Kik M, Rozendaal H, van den Kerkhof H, Beerens N. 2021. Highly pathogenic avian influenza A(H5N1) virus in wild red foxes, the Netherlands, 2021. Emerging Infectious Diseases, 27, 2960–2962. 
Shi J, Deng G, Liu P, Zhou J, Guan L, Li W, Li X, Guo J, Wang G, Fan J, Wang J, Li Y, Jiang Y, Liu L, Tian G, Li C, Chen H. 2013. Isolation and characterization of H7N9 viruses from live poultry markets - Implication of the source of current H7N9 infection in humans. Chinese Science Bulletin, 58, 1857–1863. 
Shi J, Deng G, Ma S, Zeng X, Yin X, Li M, Zhang B, Cui P, Chen Y, Yang H, Wan X, Liu L, Chen P, Jiang Y, Guan Y, Liu J, Gu W, Han S, Song Y, Liang L, et al. 2018. Rapid evolution of H7N9 highly pathogenic viruses that emerged in China in 2017. Cell Host & Microbe, 24, 558–568.e7.
Swayne D E. 2012. Impact of vaccines and vaccination on global control of avian influenza. Avian Diseases, 56, 818–828.
Tian G, Zhang S, Li Y, Bu Z, Liu P, Zhou J, Li C, Shi J, Yu K, Chen H. 2005. Protective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine developed by reverse genetics. Virology, 341, 153–162.
WHO (World Health Organization). 2008. Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1). Emerging Infectious Diseases, 14, e1.
WHO (World Health Organization). 2011. Manual for the laboratory diagnosis and virological surveillance of influenza. [2021-2-2]. https://apps.who.int/iris/bitstream/handle/10665/44518/9789241548090_eng.pdf?sequence=1
WHO (World Health Organization). 2020. Antigenic and genetic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness. [2021-4-8]. https://apps.who.int/iris/handle/10665/336259
Wu J, Ke C, Lau E H Y, Song Y, Cheng K L, Zou L, Kang M, Song T, Peiris M, Yen H L. 2019. Influenza H5/H7 virus vaccination in poultry and reduction of zoonotic infections, Guangdong Province, China, 2017–18. Emerging Infectious Diseases, 25, 116–118.
Yin X, Deng G, Zeng X, Cui P, Hou Y, Liu Y, Fang J, Pan S, Wang D, Chen X, Zhang Y, Wang X, Tian G, Li Y, Chen Y, Liu L, Suzuki Y, Guan Y, Li C, Shi J, et al. 2021. Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China. PLoS Pathogens, 17, e1009561.
Zeng X, Chen X, Ma S, Wu J, Bao H, Pan S, Liu Y, Deng G, Shi J, Chen P, Jiang Y, Li Y, Hu J, Lu T, Mao S, Guo S, Liu J, Tian G, Chen H. 2020. Protective efficacy of an H5/H7 trivalent inactivated vaccine produced from Re-11, Re-12, and H7-Re2 strains against challenge with different H5 and H7 viruses in chickens. Journal of Integrative Agriculture, 19, 2294–300.
Zeng X, Tian G, Shi J, Deng G, Li C, Chen H. 2018. Vaccination of poultry successfully eliminated human infection with H7N9 virus in China. Science China (Life Sciences), 61, 1465–1473.
Zhang Q, Shi J, Deng G, Guo J, Zeng X, He X, Kong H, Gu C, Li X, Liu J, Wang G, Chen Y, Liu L, Liang L, Li Y, Fan J, Wang J, Li W, Guan L, Li Q, et al. 2013. H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science, 341, 410–414.

[1] Libin Liang, Yaning Bai, Wenyan Huang, Pengfei Ren, Xing Li, Dou Wang, Yuhan Yang, Zhen Gao, Jiao Tang, Xingchen Wu, Shimin Gao, Yanna Guo, Mingming Hu, Zhiwei Wang, Zhongbing Wang, Haili Ma, Junping Li. Genetic and biological properties of H9N2 avian influenza viruses isolated in central China from 2020 to 2022[J]. >Journal of Integrative Agriculture, 2024, 23(8): 2778-2791.
[2] Zenglei Hu, Ya Huang, Jiao Hu, Xiaoquan Wang, Shunlin Hu, Xiufan Liu.

Antibodies elicited by Newcastle disease virus-vectored H7N9 avian influenza vaccine are functional in activating the complement system [J]. >Journal of Integrative Agriculture, 2024, 23(6): 2052-2064.

[3] Xianying Zeng, Jianzhong Shi, Hualan Chen.

Control of highly pathogenic avian influenza through vaccination [J]. >Journal of Integrative Agriculture, 2024, 23(5): 1447-1453.

[4] Lingzhai Meng, Mengmeng Yu, Suyan Wang, Yuntong Chen, Yuanling Bao, Peng Liu, Xiaoyan Feng, Tana He, Ru Guo, Tao Zhang, Mingxue Hu, Changjun Liu, Xiaole Qi, Kai Li, Li Gao, Yanping Zhang, Hongyu Cui, Yulong Gao.

A novel live attenuated vaccine candidate protects chickens against subtype B avian metapneumovirus [J]. >Journal of Integrative Agriculture, 2024, 23(5): 1658-1670.

[5] LIU Li-ling, YANG Huan-liang, GUO Fu-sheng, WANG Xiu-rong, DENG Guo-hua, SHI Jian-zhong, TIAN Guo-bin, ZENG Xian-ying. Emergence of H5N1 highly pathogenic avian influenza in Democratic People’s Republic of Korea[J]. >Journal of Integrative Agriculture, 2022, 21(5): 1534-1538.
[6] ZENG Xian-ying, CHEN Xiao-han, MA Shu-jie, WU Jiao-jiao, BAO Hong-mei, PAN Shu-xin, LIU Yan-jing, DENG Guo-hua, SHI Jian-zhong, CHEN Pu-cheng, JIANG Yong-ping, LI Yan-bing, HU Jing-lei, LU Tong, MAO Sheng-gang, GUO Xing-fu, LIU Jing-li, TIAN Guo-bin, CHEN Hua-lan. Protective efficacy of an H5/H7 trivalent inactivated vaccine produced from Re-11, Re-12, and H7-Re2 strains against challenge with different H5 and H7 viruses in chickens[J]. >Journal of Integrative Agriculture, 2020, 19(9): 2294-2300.
[7] SHI Lin, YU Xue-wu, YAO Wei, YU Ben-liang, HE Li-kun, GAO Yuan, ZHANG Yun-xian, TIAN Guo-bin, PING Ji-hui, WANG Xiu-rong. Development of a reverse-transcription loop-mediated isothermal amplification assay to detect avian influenza viruses in clinical specimens[J]. >Journal of Integrative Agriculture, 2019, 18(7): 1428-1435.
[8] CHENG Pei-pei, HU Xing-xing, WANG Chun-mei, LIU Ying-chun, WANG Mi, ZHANG Ke-yu, FEI Chenzhong, ZHANG Li-fang, WANG Xiao-yang, ZHENG Wen-li, XUE Fei-qun. Pharmacokinetics of oral ethanamizuril solution in chickens[J]. >Journal of Integrative Agriculture, 2018, 17(12): 2783-2789.
[9] HUANG Ze-ying, Adam Loch, Christopher Findlay, WANG Ji-min. Adoption of HPAI biosecurity measures: The Chinese broiler industry[J]. >Journal of Integrative Agriculture, 2017, 16(01): 181-189.
[10] WEI Yan-di, GAO Wei-hua, SUN Hong-lei, YU Chen-fang, PEI Xing-yao, Sun Yi-peng, LIU Jin-hua, PU Juan. A duplex RT-PCR assay for detection of H9 subtype avian influenza viruses and infectious bronchitis viruses[J]. >Journal of Integrative Agriculture, 2016, 15(9): 2105-2113.
[11] Chang-Yong Choi, John Y Takekawa, XIONG Yue, LIU Ying, Martin Wikelski, George Heine, Diann J Prosser, Scott H Newman, John Edwards, Fusheng Guo, Xiangming Xiao. Tracking domestic ducks: A novel approach for documenting poultry market chains in the context of avian influenza transmission[J]. >Journal of Integrative Agriculture, 2016, 15(7): 1584-1594.
[12] SU Xiao-na, XIE Qing-mei, LIAO Chang-tao, YAN Zhuan-qiang, CHEN Wei-guo, BI Ying-zuo, CHEN Feng. Sequence and phylogenetic analysis of hemagglutinin genes of H9N2 influenza viruses isolated from chicken in China from 2013 to 2015[J]. >Journal of Integrative Agriculture, 2016, 15(11): 2604-2612.
[13] Jianhong E Mu, Bruce A McCarl, Amy Hagerman, David Bessler. Impacts of bovine spongiform encephalopathy and avian influenza on U.S. meat demand[J]. >Journal of Integrative Agriculture, 2015, 14(6): 1130-1141.
[14] SHI Ping, Shu Geng, LI Ting-ting, LI Yu-shui, FENG Ting, WU Hua-nan. Methods to detect avian influenza virus for food safety surveillance[J]. >Journal of Integrative Agriculture, 2015, 14(11): 2296-2308.
[15] ZHAO Guang-wei, SHEN Bo, XIE Qing, XU Li-xin, YAN Ruo-feng, SONG Xiao-kai, Hassan Ibrahim Adam, LI Xiang-rui. Isolation and Molecular Characterization of Toxoplasma gondii from Chickens in China[J]. >Journal of Integrative Agriculture, 2012, 12(8): 1347-1353.
No Suggested Reading articles found!