Abstract
SummarySARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
Highlights
In the past two decades, there have been zoonotic transmissions of three highly pathogenic coronaviruses—SARS-CoV-1, MERS-CoV, and SARS-CoV-2—which have caused widespread human disease
Hamsters, and non-human primates strongly suggest that neutralizing antibodies isolated from infected patients can protect infection and, in the case of established infection, can reduce viremia and mitigate the development of clinical symptoms (Baum et al, 2020b; Cao et al, 2020a; Mercado et al, 2020; Rogers et al, 2020a; Schafer et al, 2021; Shi et al, 2020; Tortorici et al, 2020; Wu et al, 2020; Yu et al, 2020)
Serum Ab titers and neutralizing activities against SARS-CoV-2 Peripheral blood mononuclear cells (PBMCs) and serum or plasma were collected from four SARS-CoV-2-infected adults (CV1 [previously discussed in Seydoux et al, 2020], CV2, CV3, and PCV1) at 3, 3.5, 6, and 7 weeks after the onset of symptoms, respectively (Table S1)
Summary
In the past two decades, there have been zoonotic transmissions of three highly pathogenic coronaviruses—SARS-CoV-1, MERS-CoV, and SARS-CoV-2—which have caused widespread human disease. Hamsters, and non-human primates strongly suggest that neutralizing antibodies (nAbs) isolated from infected patients can protect infection and, in the case of established infection, can reduce viremia and mitigate the development of clinical symptoms (Baum et al, 2020b; Cao et al, 2020a; Mercado et al, 2020; Rogers et al, 2020a; Schafer et al, 2021; Shi et al, 2020; Tortorici et al, 2020; Wu et al, 2020; Yu et al, 2020). NAbs are believed to be an important component of the protective immune responses elicited by effective vaccines. Both the mRNA-based Pfizer and Moderna vaccines elicit potent serum neutralizing Ab responses against SARS-CoV-2 (Jackson et al, 2020; Walsh et al, 2020)
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