Design of a Mutation-integrated Trimeric RBD with Broad Protection Against SARS-CoV-2

Overview

Journal Cell Discov

Date 2022 Feb 16

PMID 35169113

Authors

Yu Liang

Jing Zhang

Run Yu Yuan

Mei Yu Wang

Peng He

Ji Guo Su

Zi Bo Han

Yu Qin Jin

Jun Wei Hou

Hao Zhang

Xue Feng Zhang

Shuai Shao

Ya Nan Hou

Zhao Ming Liu

Li Fang Du

Fu Jie Shen

Wei Min Zhou

Ke Xu

Ru Qin Gao

Fang Tang

Ze Hua Lei

Shuo Liu

Wei Zhen

Jin Juan Wu

Xiang Zheng

Ning Liu

Shi Chen

Zhi Jing Ma

Fan Zheng

Si Yu Ren

Zhong Yu Hu

Wei Jin Huang

Gui Zhen Wu

Chang Wen Ke

Qi Ming Li

Affiliations

Soon will be listed here.

Abstract

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.

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