Wu Kai, Werner Anne P, Moliva Juan I, Koch Matthew, Choi Angela, Stewart-Jones Guillaume B E, Bennett Hamilton, Boyoglu-Barnum Seyhan, Shi Wei, Graham Barney S, Carfi Andrea, Corbett Kizzmekia S, Seder Robert A, Edwards Darin K
bioRxiv. 2021 Jan 25:2021.01.25.427948. doi: 10.1101/2021.01.25.427948.
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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一场全球大流行的致病性感染源，已导致全球超过200万人死亡。Moderna mRNA-1273疫苗在3期研究中显示出约94%的疗效，并已获得紧急使用授权。在刺突蛋白中发生突变的SARS-CoV-2变体的出现，最近在英国（B.1.1.7）和南非共和国（B.1.351）流行的分离株，导致通过假病毒中和（PsVN）试验检测到的康复期血清中和作用降低，以及对某些单克隆抗体产生抗性。在这里，我们使用两种正交的水泡性口炎病毒（VSV）和慢病毒PsVN试验，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灵长类动物（NHP）血清的中和能力。在这两种情况下，均未检测到对B.1.1.7变体中和作用的显著影响，然而，针对B.1.351中存在的突变，中和作用有所降低。在使用D614G刺突的VSV PsVN试验中，来自临床试验参与者的人类血清的几何平均滴度（GMT）为1/1852。与D614G VSV假病毒相比，含有K417N-E484K-N501Y-D614G和完整B.1.351突变的刺突的VSV假病毒分别导致GMT降低2.7倍和6.四倍。重要的是，这些人类血清对完整B.1.351刺突变体的VSV PsVN GMT仍为1/290，所有评估血清均能完全中和。同样，用30或100μg mRNA-1273免疫的NHP血清对完整B.1.351刺突变体的VSV PsVN GMT分别约为1/323或1/404，与D614G相比降低了约5至10倍。在VSV或慢病毒PsVN试验中测试时，B.1.1.7和B.1.351变体特有的单个突变对中和作用有类似影响。尽管观察到中和作用下降，但人类疫苗接种者血清中针对B.1.351变体的VSV PsVN滴度的GMT仍保持在约1/300。综上所述，这些数据表明，mRNA-1273疫苗接种后，对完整B.1.351变体的中和作用有所降低，但仍然显著。
