Abstract

To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1 (dominant variant identified in the current India outbreak) on the infectivity and neutralization activities of the immune sera, L452R and E484Q (L452R-E484Q variant), pseudotyped virus was constructed (with the D614G background). The impact on binding with the neutralizing antibodies was also assessed with an ELISA assay. Pseudotyped virus carrying a L452R-E484Q variant showed a comparable infectivity compared with D614G. However, there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant receptor binding domain (RBD) protein, convalescent patients, and healthy vaccinees vaccinated with an mRNA vaccine. In addition, there was a reduction in binding of L452R-E484Q-D614G protein to the antibodies of the immune sera from vaccinated non-human primates. These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2. Reduced neutralization activities against the L452R-E484Q variant will have an impact on health authority planning and implications for the vaccination strategy/new vaccine development.

Details

Title
The SARS-CoV-2 spike L452R-E484Q variant in the Indian B.1.617 strain showed significant reduction in the neutralization activity of immune sera
Author
Li, Gen 1 ; Zhou, Zhongcheng 1 ; Du, Peng 1 ; Yu, Meixing 1 ; Li, Ning 1 ; Xiong, Xinxin 1 ; Huang, Hong 1 ; Liu, Zhihai 1 ; Dai, Qinjin 1 ; Zhu, Jie 1 ; Guo, Chengbin 1 ; Wu, Shanyun 1 ; Baptista-Hon, Daniel T 2   VIAFID ORCID Logo  ; Miao, Man 2 ; Lam, Wai Ming 2 ; Wu, Yong 3 ; Zeng, Fanxin 4 ; Zhang, Charlotte L 1 ; Zhang, Edward D 1 ; Song, Haifeng 5 ; Liu, Jianghai 6 ; Johnson Yiu-Nam Lau 7 ; Xiang, Andy P 8 ; Zhang, Kang 1 

1  Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou 510620, China 
2  University Hospital and Center for Biomedicine and Innovations, Faculty of Medicine, Macau University of Science and Technology , Macau 030027, China 
3  Jinan University First Affiliated Hospital, Jinan University , Guangzhou 510630, China 
4  Department of Clinical Research Center , Dazhou Central Hospital, Dazhou 635099, China 
5  Department of Bioinformatics and AI, Bioland Laboratory , Guangzhou 510000, China 
6  ABLINK Biotech Co. , Chengdu 610000, China 
7  Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University , Hung Hom, Hong Kong 610051, China 
8  Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University , Guangzhou 510000, China 
Pages
149-154
Publication year
2021
Publication date
Sep 2021
Publisher
Oxford University Press
ISSN
20965303
e-ISSN
25161571
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1093/pcmedi/pbab016
ProQuest document ID
3171416820
Copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.