Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 180 million people since its identification as the cause of the current COVID-19 pandemic. The rapid pace of vaccine development has resulted in multiple vaccines already in use worldwide. The contemporaneous emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales underscores the need to monitor the efficacy of vaccines being administered globally. All WHO designated VOC carry spike (S) polymorphisms thought to enable escape from neutralizing antibodies. Here, we characterize the neutralizing activity of post-Sputnik V vaccination sera against the ensemble of S mutations present in alpha (B.1.1.7) and beta (B.1.351) VOC. Using de novo generated replication-competent vesicular stomatitis virus expressing various SARS-CoV-2-S in place of VSV-G (rcVSV-CoV2-S), coupled with a clonal 293T-ACE2 + TMPRSS2 + cell line optimized for highly efficient S-mediated infection, we determine that only 1 out of 12 post-vaccination serum samples shows effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralize S from B.1.1.7 and exhibit only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 180 million people since its identification as the cause of the current COVID-19 pandemic
Several groups have generated replicationcompetent VSV expressing SARS-CoV-2 spike in place of VSVG35–38. These rcVSV-CoV2-S can be used in BSL-2 compatible virus neutralization assays (VNAs), which correlate very well with VNAs using live SARS-CoV-2 (Spearman’s r > 0.9 across multiple studies). rcVSV-CoV2-S has been assessed as a candidate vaccine[37,39], and used in forward genetics experiments to generate antibody escape mutants or perform comprehensive epitope mapping studies[20,38,40]
A key public health concern related to emergent SARS-CoV-2 variants is that by incrementally accruing mutations that escape neutralizing antibodies, they will penetrate herd immunity and spread to reach unvaccinated individuals, some of whom will be susceptible to severe or fatal disease
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 180 million people since its identification as the cause of the current COVID-19 pandemic. CoV-2 is closely related to two other zoonotic betacoronaviruses, MERS-CoV and SARS-CoV, that cause life-threatening respiratory infections[3]. This global health emergency has spurred the development of COVID-19 preventive vaccines at an unprecedented pace. Six are already authorized for human use across the globe[4,5,6,7,8,9] These vaccines focus on the SARS-CoV-2 spike protein (S), due to its critical roles in cell entry. The presence of serum neutralizing antibodies directed at S correlate strongly with protection against COVID-1910,11 These six vaccines are efficacious, the recent emergence of SARS-CoV-2 variants has reignited concerns that the pandemic may not be so brought under control. The B.1.1.7 lineage has been shown to exhibit enhanced transmissibility[14] as well as an increased case fatality rate[15,16]
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