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Abstract
Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.
Highlights
Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority
Using a high-throughput rapid system for antibody discovery, we isolated more than 1000 monoclonal antibodies (mAbs) from three convalescent donors by memory B cell selection using SARS-CoV-2 S or receptor binding domain (RBD) recombinant proteins
A range of neutralizing antibodies (nAbs) were isolated to different sites on the S protein
Summary
Two platforms were established to evaluate plasma neutralization activity against SARSCoV-2, one using replication-competent virus and another using pseudovirus (PSV). Donor plasma were tested for binding to recombinant SARSCoV-2 and SARS-CoV-1 S and receptor binding domain (RBD) proteins, for binding to cell surface– expressed spikes, and for neutralization in both live replicating virus and PSV assays [Fig. 2, B to D, and fig. The bulk-transformed ligation products for both the heavy chain and light chain were transfected and tested for binding to RBD and S protein and for neutralization in the SARS-CoV-2 PSV assay using HeLa-ACE2 target cells Indicate comparable viral loads between the three higher doses (2 mg, 500 mg, and 125 mg) of nAbs. In contrast, equivalent viral loads were observed between the control group receiving Den and the low-dose groups receiving 31 or 8 mg of nAb. In contrast to the nAb to RBD-A, the less potent and incompletely neutralizing antibody to the S-B epitope showed no evidence of protection at any concentration when compared with control animals Sterilizing immunity at serum concentrations that represent a large multiplier of the in vitro neutralizing IC50 is observed for many viruses [11]
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