Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative infection of a global pandemic that has led to more than 2 million deaths worldwide. The Moderna mRNA-1273 vaccine has demonstrated ~94% efficacy in a Phase 3 study and has been approved under Emergency Use Authorization. The emergence of SARS-CoV-2 variants with mutations in the spike protein, most recently circulating isolates from the United Kingdom (B.1.1.7) and Republic of South Africa (B.1.351), has led to lower neutralization from convalescent serum by pseudovirus neutralization (PsVN) assays and resistance to certain monoclonal antibodies. Here, using two orthogonal VSV and lentivirus PsVN assays expressing spike variants of 20E (EU1), 20A.EU2, D614G-N439, mink cluster 5, B.1.1.7, and B.1.351 variants, we assessed the neutralizing capacity of sera from human subjects or non-human primates (NHPs) that received mRNA-1273. No significant impact on neutralization against the B.1.1.7 variant was detected in either case, however reduced neutralization was measured against the mutations present in B.1.351. Geometric mean titer (GMT) of human sera from clinical trial participants in VSV PsVN assay using D614G spike was 1/1852. VSV pseudoviruses with spike containing K417N-E484K-N501Y-D614G and full B.1.351 mutations resulted in 2.7 and 6.4-fold GMT reduction, respectively, when compared to the D614G VSV pseudovirus. Importantly, the VSV PsVN GMT of these human sera to the full B.1.351 spike variant was still 1/290, with all evaluated sera able to fully neutralize. Similarly, sera from NHPs immunized with 30 or 100μg of mRNA-1273 had VSV PsVN GMTs of ~ 1/323 or 1/404, respectively, against the full B.1.351 spike variant with a ~ 5 to 10-fold reduction compared to D614G. Individual mutations that are characteristic of the B.1.1.7 and B.1.351 variants had a similar impact on neutralization when tested in VSV or in lentivirus PsVN assays. Despite the observed decreases, the GMT of VSV PsVN titers in human vaccinee sera against the B.1.351 variant remained at ~1/300. Taken together these data demonstrate reduced but still significant neutralization against the full B.1.351 variant following mRNA-1273 vaccination.

中文翻译：

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mRNA-1273疫苗诱导针对全球SARS-CoV-2变体的穗突变体的中和抗体

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）是全球大流行的致病性感染，已导致全球200万人死亡。Moderna mRNA-1273疫苗在3期研究中显示约94％的功效，并已获得紧急使用授权批准。SARS-CoV-2变异体的出现，其刺突蛋白中有突变，最近一次从英国（B.1.1.7）和南非共和国（B.1.351）传播的分离株导致恢复期血清中和的降低通过伪病毒中和（PsVN）分析和对某些单克隆抗体的抗性。在这里，使用两个正交的VSV和慢病毒PsVN分析表达20E（EU1），20A.EU2，D614G-N439，水貂簇5，B.1.1.7和B.1.351变体的刺突变体，我们评估了接受mRNA-1273的人类受试者或非人类灵长类动物（NHP）血清的中和能力。在两种情况下均未检测到针对B.1.1.7变体的中和作用的显着影响，但是针对B.1.351中存在的突变测得的中和度降低。使用D614G穗进行VSV PsVN分析的临床试验参与者的人血清几何平均滴度（GMT）为1/1852。与D614G VSV伪病毒相比，带有包含K417N-E484K-N501Y-D614G和完整B.1.351突变的穗的VSV伪病毒分别导致GMT降低2.7倍和6.4倍。重要的是，这些人类血清对完整的B.1.351穗突变体的VSV PsVN GMT仍为1/290，所有评估的血清都能够完全中和。同样，相对于完整的B.1.351刺突变体，用30或100μgmRNA-1273免疫的NHP血清的VSV PsVN GMT分别为〜1/323或1/404，与D614G相比降低了约5至10倍。在VSV或慢病毒PsVN分析中进行测试时，具有B.1.1.7和B.1.351变体特征的单个突变对中和具有类似的影响。尽管观察到了下降，但针对B.1.351变异体的人疫苗血清中VSV PsVN滴度的GMT仍为〜1/300。综上所述，这些数据证明了在mRNA-1273疫苗接种后，针对完整的B.1.351变体的中和减少，但仍然很明显。在VSV或慢病毒PsVN分析中测试时，351个变体对中和有相似的影响。尽管观察到了下降，但针对B.1.351变异体的人疫苗血清中VSV PsVN滴度的GMT仍为〜1/300。综上所述，这些数据证明了在mRNA-1273疫苗接种后，针对完整的B.1.351变体的中和减少，但仍然很明显。在VSV或慢病毒PsVN分析中测试时，351个变体对中和有相似的影响。尽管观察到了下降，但针对B.1.351变异体的人疫苗血清中VSV PsVN滴度的GMT仍为〜1/300。综上所述，这些数据证明了在mRNA-1273疫苗接种后，针对完整的B.1.351变体的中和减少，但仍然很明显。