JIA-2022-0488 新型H5+H7三价灭活疫苗（H5-Re13株+H5-Re14株+H7-Re4株）免疫鸡、鸭、鹅后可对不同分支的H5和H7N9病毒提供完全保护

doi:10.1016/S2095-3119(22)63904-2

Journal of Integrative Agriculture ›› 2022, Vol. 21 ›› Issue (7): 2086-2094.DOI: 10.1016/S2095-3119(22)63904-2

JIA-2022-0488 新型H5+H7三价灭活疫苗（H5-Re13株+H5-Re14株+H7-Re4株）免疫鸡、鸭、鹅后可对不同分支的H5和H7N9病毒提供完全保护

收稿日期:2022-04-14 接受日期:2022-04-23 出版日期:2022-07-01 发布日期:2022-04-23

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

Received:2022-04-14 Accepted:2022-04-23 Online:2022-07-01 Published:2022-04-23
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.
Supported by:
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).

摘要/Abstract

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.

Key words: avian influenza , H5/H7 trivalent vaccine , H5-Re13 , H5-Re14 , H7-Re4 strains , protective efficacy , chickens , ducks and geese

. JIA-2022-0488 新型H5+H7三价灭活疫苗（H5-Re13株+H5-Re14株+H7-Re4株）免疫鸡、鸭、鹅后可对不同分支的H5和H7N9病毒提供完全保护[J]. Journal of Integrative Agriculture, 2022, 21(7): 2086-2094.

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. 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[J]. Journal of Integrative Agriculture, 2022, 21(7): 2086-2094.

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JIA-2022-0488 新型H5+H7三价灭活疫苗（H5-Re13株+H5-Re14株+H7-Re4株）免疫鸡、鸭、鹅后可对不同分支的H5和H7N9病毒提供完全保护

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

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