Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2

Cell Discovery

Run Yu Yuan¹  Chang Wen Ke¹  Shuo Liu²  Mei Yu Wang²  Zhong Yu Hu²  Peng He²  Wei Jin Huang²  Ke Xu³  Wei Min Zhou³  Gui Zhen Wu³  Wei Zhen³  Ru Qin Gao⁴  Shuai Shao⁵  Yu Liang⁵  Ning Liu⁵  Jun Wei Hou⁵  Jing Zhang⁵  Xue Feng Zhang⁵  Zhao Ming Liu⁵  Li Fang Du⁵  Yu Qin Jin⁵  Shi Chen⁵  Qi Ming Li⁵  Zi Bo Han⁵  Zhi Jing Ma⁵  Ya Nan Hou⁵  Hao Zhang⁵  Ze Hua Lei⁵  Ji Guo Su⁵  Fang Tang⁵  Fu Jie Shen⁵  Fan Zheng⁵  Jin Juan Wu⁵  Xiang Zheng⁵  Si Yu Ren⁵ 

[1] Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong, China;National Institute for Food and Drug Control (NIFDC), Beijing, China;National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China;Qingdao Centers for Disease Control and Prevention, Qingdao, Shandong, China;The Sixth Laboratory, National Vaccine and Serum Institute (NVSI), Beijing, China;National Engineering Center for New Vaccine Research, Beijing, China;

DOI  :  10.1038/s41421-022-00383-5

来源: Springer

【 摘 要 】

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

【 授权许可】

CC BY