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

Li, Gen; Zhou, Zhongcheng; Du, Peng; Yu, Meixing; Li, Ning; Xiong, Xinxin; Huang, Hong; Liu, Zhihai; Dai, Qinjin; Zhu, Jie; Guo, Chengbin; Wu, Shanyun; Baptista-Hon, Daniel T; Miao, Man; Ming, Lam Wai; Wu, Yong; Zeng, Fanxin; Zhang, Charlotte L; Zhang, Edward D; Song, Haifeng; Liu, Jianghai; Lau, Johnson Yiu-Nam; Xiang, Andy P; Zhang, Kang

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.