A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.
A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.
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DOI：
10.1038/s41422-022-00746-3
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发表时间：
2022-12
期刊：
影响因子：
44.1
通讯作者：
Zheng, Yong-Tang
中科院分区：
文献类型：
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作者：
Pang, Wei;Lu, Ying;Zhao, Yan-Bo;Shen, Fan;Fan, Chang-Fa;Wang, Qian;He, Wen-Qiang;He, Xiao-Yan;Li, Ze-Kai;Chen, Tao-Tao;Yang, Cui-Xian;Li, You-Zhi;Xiao, Si-Xuan;Zhao, Zu-Jiang;Huang, Xu-Sheng;Luo, Rong-Hua;Yang, Liu-Meng;Zhang, Mi;Dong, Xing-Qi;Li, Ming-Hua;Feng, Xiao-Li;Zhou, Qing-Cui;Qu, Wang;Jiang, Shibo;Ouyang, Songying;Zheng, Yong-Tang
新出现的SARS-CoV-2变异体通常在刺突蛋白的S1亚基中具有许多突变，这削弱了当前疫苗和抗体治疗的功效。这就需要针对S蛋白保守区域的SARS-CoV-2疫苗。本研究以S蛋白S2亚基中的HR 1保守结构域为靶点，设计了一种重组亚基疫苗HR 121。HR 121由HR 1-linker 1-HR 2-linker 2-HR 1组成，在构象和功能上类似于S2亚基的融合中间体构象中存在的HR 1结构域。用HR 121免疫家兔和恒河猴，可产生针对SARS-CoV-2及其变异株（特别是Omicron亚系）的高效交叉中和抗体。HR 121疫苗接种在hACE 2转基因小鼠、叙利亚金黄仓鼠和恒河猴中实现了对原型SARS-CoV-2感染的接近完全的保护，并且在叙利亚金黄仓鼠中实现了对Omicron BA.2感染的有效保护。这项研究表明，HR 121是一个有前途的候选人的变异证明SARS-CoV-2疫苗与一个新的保守的目标，在S2亚基的应用对当前和未来的SARS-CoV-2变异。
The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.
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DOI：
10.1056/nejmoa2119451
发表时间：
2022-04-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Andrews N;Stowe J;Kirsebom F;Toffa S;Rickeard T;Gallagher E;Gower C;Kall M;Groves N;O'Connell AM;Simons D;Blomquist PB;Zaidi A;Nash S;Iwani Binti Abdul Aziz N;Thelwall S;Dabrera G;Myers R;Amirthalingam G;Gharbia S;Barrett JC;Elson R;Ladhani SN;Ferguson N;Zambon M;Campbell CNJ;Brown K;Hopkins S;Chand M;Ramsay M;Lopez Bernal J
通讯作者：
Lopez Bernal J
影响因子：
30.3
作者：
Ai, Jingwen;Wang, Xun;He, Xinyi;Zhao, Xiaoyu;Zhang, Yi;Jiang, Yuchao;Li, Minghui;Cui, Yuchen;Chen, Yanjia;Qiao, Rui;Li, Lin;Yang, Lulu;Li, Yi;Hu, Zixin;Zhang, Wenhong;Wang, Pengfei
通讯作者：
Wang, Pengfei
影响因子：
56.9
作者：
Cai, Yongfei;Zhang, Jun;Chen, Bing
通讯作者：
Chen, Bing
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1126/science.abq3773
发表时间：
2022-08-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
通讯作者：
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