Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.
Highlights
As the causative agent of COVID-19, SARS-CoV-2 has caused a global pandemic with more than 211.28 million cases and 4.42 million fatalities as of August 24, 2021 [1]
We examined the binding activity of antibodies that bind to the receptor binding domain (RBD) protein of WT SARS-CoV-2 strain and the mutated RBD proteins of SARS-CoV-2 VOCs (Figure 1A) in the convalescent sera of WT SARS-CoV-2-infected patients by IgG ELISA
Binding ability of convalescent sera from COVID-19 patients with severe illness against SARS-CoV-2 VOCs, albeit blunted, was superior to those of COVID-19 patients with moderate or mild/asymptomatic illness (Supplementary Figures S1A–E). These results suggest a crucial role of residues N501, E484, L452, and K417 in epitope regions of high-affinity antibodies specific for SARS-CoV-2 RBD
Summary
As the causative agent of COVID-19, SARS-CoV-2 has caused a global pandemic with more than 211.28 million cases and 4.42 million fatalities as of August 24, 2021 [1]. The SARS-CoV-2 utilizes its spike (S) protein, including the surface subunit S1 and the transmembrane subunit S2, for receptor binding and virus entry. One major concern is the emergence of SARS-CoV-2 variants of concern (VOCs), in particular, with mutation(s) located in the RBD region [7, 8]. These SARS-CoV-2 VOCs threaten efforts to contain the COVID-19 pandemic and include B.1.1.7 (N501Y in RBD) [9], B.1.351 (K417N, E484K, and N501Y in RBD) [10], P.1 (K417T, E484K and N501Y in RBD) [11], and B.1.617.1 (L452R and E484Q in RBD) [12]. We profiled the neutralizing capacity of one previously reported VH3-30 monoclonal antibody (mAb) against SARS-CoV2 VOCs and non-VOC variants
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