Tada Takuya, Zhou Hao, Dcosta Belinda M, Samanovic Marie I, Mulligan Mark J, Landau Nathaniel R
Department of Microbiology, NYU Grossman School of Medicine, 430 East 29th Street, Alexandria West Building, New York, NY 10016, USA.
NYU Langone Vaccine Center and Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA.
iScience. 2021 Nov 19;24(11):103341. doi: 10.1016/j.isci.2021.103341. Epub 2021 Oct 24.
Highly transmissible SARS-CoV-2 variants identified in India and designated B.1.617, Kappa (B.1.617.1), Delta (B.1.617.2), B.1.618, and B.1.36.29 contain spike mutations L452R, T478K, E484K, E484Q, and N440K located within the spike receptor-binding domain and thus could contribute to increased transmissibility and potentially allow re-infection or cause resistance to vaccine-elicited antibody. To address these issues, we used lentiviruses pseudotyped by variant spikes to measure their neutralization by convalescent sera, vaccine-elicited and Regeneron therapeutic antibodies, and ACE2 affinity. Convalescent sera and vaccine-elicited antibodies neutralized viruses with Delta spike with 2- to 5-fold decrease in titer in different donors. Regeneron antibody cocktail neutralized virus with the Delta spike with a 2.6-fold decrease in titer. Neutralization resistance to serum antibodies and monoclonal antibodies was mediated by L452R mutation. These relatively modest decreases in antibody neutralization titer for viruses with variant spike proteins suggest that current vaccines will remain protective against the family of Delta variants.
在印度发现的高传播性严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变体,命名为B.1.617、卡帕(B.1.617.1)、德尔塔(B.1.617.2)、B.1.618和B.1.36.29,其刺突蛋白受体结合域内含有L452R、T478K、E484K、E484Q和N440K等刺突突变,因此可能导致传播性增加,并可能导致再次感染或对疫苗诱导的抗体产生抗性。为了解决这些问题,我们使用由变体刺突蛋白假型化的慢病毒来测量康复期血清、疫苗诱导的抗体、Regeneron治疗性抗体对其的中和作用以及与血管紧张素转换酶2(ACE2)的亲和力。康复期血清和疫苗诱导的抗体对带有德尔塔刺突蛋白的病毒进行中和时,不同供体的效价降低了2至5倍。Regeneron抗体鸡尾酒对带有德尔塔刺突蛋白的病毒进行中和时,效价降低了2.6倍。对血清抗体和单克隆抗体的中和抗性由L452R突变介导。对于带有变体刺突蛋白的病毒,抗体中和效价的这些相对适度的降低表明,目前的疫苗对德尔塔变体家族仍将具有保护作用。