Tada Takuya, Dcosta Belinda M, Samanovic-Golden Marie, Herati Ramin S, Cornelius Amber, Mulligan Mark J, Landau Nathaniel R
bioRxiv. 2021 Feb 7:2021.02.05.430003. doi: 10.1101/2021.02.05.430003.
The increasing prevalence of SARS-CoV-2 variants with mutations in the spike protein has raised concerns that recovered individuals may not be protected from reinfection and that current vaccines will become less effective. The B.1.1.7 isolate identified in the United Kingdom and B.1.351 isolate identified in the Republic of South Africa encode spike proteins with multiple mutations in the S1 and S2 subunits. In addition, variants have been identified in Columbus, Ohio (COH.20G/677H), Europe (20A.EU2) and in domesticated minks. Analysis by antibody neutralization of pseudotyped viruses showed that convalescent sera from patients infected prior to the emergence of the variant viruses neutralized viruses with the B.1.1.7, B.1.351, COH.20G/677H Columbus Ohio, 20A.EU2 Europe and mink cluster 5 spike proteins with only a minor decrease in titer compared to that of the earlier D614G spike protein. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus and neutralized virus with the B.1.351 spike with, on average, a 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). The reduction in titer was attributable to the E484K mutation in the RBD. The B.1.1.7 and B.1.351 viruses were not more infectious than D614G on ACE2.293T cells but N501Y, an ACE2 contacting residue present in the B.1.1.7, B.1.351 and COH.20G/677H spike proteins caused higher affinity binding to ACE2, likely contributing to their increased transmissibility. These findings suggest that antibodies elicited by primary infection and by the BNT162b2 mRNA vaccine are likely to maintain protective efficacy against B.1.1.7 and most other variants but that the partial resistance of virus with the B.1.351 spike protein could render some individuals less well protected, supporting a rationale for the development of modified vaccines containing E484K.
刺突蛋白发生突变的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的流行率不断上升，引发了人们对康复个体可能无法免受再次感染以及当前疫苗效力可能降低的担忧。在英国发现的B.1.1.7毒株和在南非共和国发现的B.1.351毒株编码的刺突蛋白在S1和S2亚基中有多个突变。此外，在俄亥俄州哥伦布市（COH.20G/677H）、欧洲（20A.EU2）以及养殖水貂中也发现了变体。对假型病毒进行抗体中和分析表明，变体病毒出现之前感染的患者的康复血清对具有B.1.1.7、B.1.351、俄亥俄州哥伦布市COH.20G/677H、欧洲20A.EU2和水貂簇5刺突蛋白的病毒具有中和作用，与早期的D614G刺突蛋白相比，滴度仅略有下降。接种BNT162b2 mRNA疫苗的个体的血清标本对D614G病毒的中和滴度平均比康复血清高7倍。疫苗诱导产生的抗体对具有B.1.1.7刺突蛋白的病毒的中和滴度与D614G病毒相似，对具有B.1.351刺突蛋白的病毒的中和滴度平均降低了3倍（1:500），但该滴度仍高于康复血清对D614G的平均中和滴度（1:139）。滴度降低归因于受体结合域（RBD）中的E484K突变。在ACE2.293T细胞上，B.1.1.7和B.1.351病毒的传染性并不比D614G病毒更强，但B.1.1.7、B.1.351和COH.20G/677H刺突蛋白中存在的与ACE2接触的残基N501Y导致与ACE2的结合亲和力更高，这可能有助于它们传播性的增加。这些发现表明，初次感染和BNT162b2 mRNA疫苗诱导产生的抗体可能对B.1.1.7和大多数其他变体保持保护效力，但具有B.1.351刺突蛋白的病毒的部分抗性可能会使一些个体的保护效果较差，这为开发含有E484K的改良疫苗提供了理论依据。
