A combination vaccine against SARS-CoV-2 and H1N1 influenza based on receptor binding domain trimerized by six-helix bundle fusion core.
A combination vaccine against SARS-CoV-2 and H1N1 influenza based on receptor binding domain trimerized by six-helix bundle fusion core.
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基于六螺旋束融合核心三聚化受体结合域的 SARS-CoV-2 和 H1N1 流感联合疫苗
DOI：
10.1016/j.ebiom.2022.104297
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发表时间：
2022-11
期刊：
影响因子：
11.1
通讯作者：
Yan, Jinghua
中科院分区：
文献类型：
--
作者：
Shi, Rui;Zeng, Jiawei;Xu, Ling;Wang, Fengze;Duan, Xiaomin;Wang, Yue;Wu, Zheng;Yu, Dandan;Huang, Qingrui;Yao, Yong-Gang;Yan, Jinghua
同时或相继感染SARS-CoV-2和甲型流感病毒（IAV）导致的严重发病率和死亡率增加，特别是在老年和肥胖患者中，突出了开发针对COVID-19和流感的联合疫苗的紧迫性。在融合后构象的稳定融合核心上，构建了自组装SARS-CoV-2 RBD-三聚体和流感H1N1 HA 1-三聚体抗原。在小鼠中评价SARS-CoV-2 RBD-三聚体疫苗和H1N1 HA 1-三聚体抗原候选物的免疫原性。使用K18-hACE 2小鼠模型鉴定了针对SARS-CoV-2和IAV攻击的组合疫苗候选物的保护效力。所得的SARS-CoV-2的RBD-三聚体和H1N1流感的HA 1-三聚体都完全暴露受体结合基序（RBM）或受体结合位点（RBS）。两次剂量的RBD-三聚体在小鼠中诱导显著更高的结合和中和抗体滴度，以及强烈的Th 1/Th 2平衡的细胞免疫应答。类似地，证实HA 1-三聚体疫苗在小鼠中表现出强免疫原性。由RBD-三聚体和HA 1-三聚体组成的组合疫苗候选物在小鼠模型中对严格致死的SARS-CoV-2和同源H1N1流感共感染提供了高保护效力，其特征在于100%的存活率。我们的结果代表了基于三聚化受体结合结构域的组合疫苗候选物对抗COVID-19和流感共流行的概念验证。本课题得到了中国科学院战略重点研究计划（XDB 29040201）、国家自然科学基金（81830050、81901680、32070569）和中国博士后科学基金（2021 M703450）的资助。
Increasing severe morbidity and mortality by simultaneous or sequential infections with SARS-CoV-2 and influenza A viruses (IAV), especially in the elderly and obese patients, highlight the urgency of developing a combination vaccine against COVID-19 and influenza. Self-assembling SARS-CoV-2 RBD-trimer and Influenza H1N1 HA1-trimer antigens were constructed, upon the stable fusion core in post-fusion conformation. Immunogenicity of SARS-CoV-2 RBD-trimer vaccine and H1N1 HA1-trimer antigens candidates were evaluated in mice. Protection efficacy of a combination vaccine candidate against SARS-CoV-2 and IAV challenge was identified using the K18-hACE2 mouse model. Both the resultant RBD-trimer for SARS-CoV-2 and HA1-trimer for H1N1 influenza fully exposed receptor-binding motifs (RBM) or receptor-binding site (RBS). Two-dose RBD-trimer induced significantly higher binding and neutralizing antibody titers, and also a strong Th1/Th2 balanced cellular immune response in mice. Similarly, the HA1-trimer vaccine was confirmed to exhibit potent immunogenicity in mice. A combination vaccine candidate, composed of RBD-trimer and HA1-trimer, afforded high protection efficacy in mouse models against stringent lethal SARS-CoV-2 and homogenous H1N1 influenza co-infection, characterized by 100% survival rate. Our results represent a proof of concept for a combined vaccine candidate based on trimerized receptor binding domain against co-epidemics of COVID-19 and influenza. This project was funded by the Strategic Priority Research Program of CAS (XDB29040201), the National Natural Science Foundation of China (81830050, 81901680, and 32070569) and China Postdoctoral Science Foundation (2021M703450).
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DOI：
10.1056/nejmoa2107659
发表时间：
2021-09-23
期刊：
The New England journal of medicine
影响因子：
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DOI：
10.1056/nejmoa2202261
发表时间：
2022-06-02
期刊：
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影响因子：
56.9
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Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
4.6
作者：
Lee, Cheng-Chung;Yang, Chih-Ya;Wang, Andrew H-J
通讯作者：
Wang, Andrew H-J
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
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作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
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COVE Study Group