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
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510620, China.
University Hospital and Center for Biomedicine and Innovations, Faculty of Medicine, Macau University of Science and Technology, Macau 030027, China.
Precis Clin Med. 2021 Jul 30;4(3):149-154. doi: 10.1093/pcmedi/pbab016. eCollection 2021 Sep.
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.
为评估严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株B.1.617.1（在当前印度疫情中发现的主要变异株）刺突蛋白受体结合域（RBD）中的关键非同义氨基酸替换对免疫血清感染性和中和活性的影响，构建了携带L452R和E484Q（L452R-E484Q变异株）的假型病毒（具有D614G背景）。还通过酶联免疫吸附测定（ELISA）评估了其与中和抗体结合的影响。携带L452R-E484Q变异株的假型病毒与D614G相比显示出相当的感染性。然而，用重组受体结合域（RBD）蛋白接种的非人灵长类动物、康复患者以及用mRNA疫苗接种的健康接种者的免疫血清中和活性显著降低。此外，L452R-E484Q-D614G蛋白与接种过疫苗的非人灵长类动物免疫血清抗体的结合减少。这些结果突出了SARS-CoV-2自然进化过程中感染性与其他生物学因素之间的相互作用。针对L452R-E484Q变异株中和活性的降低将对卫生当局的规划以及疫苗接种策略/新疫苗研发产生影响。
