Potent neutralization of SARS-CoV-2 in vitro and in an animal model by a human monoclonal antibody.

Effective therapies are urgently needed for the SARS-CoV-2/COVID19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. One high affinity mAb, IgG1 ab1, specifically neutralized live SARS-CoV-2 with exceptional potency as measured by two different assays. It competed with human angiotensin-converting enzyme 2 (hACE2) for binding to RBD suggesting a competitive mechanism of virus neutralization. IgG1 ab1 protected transgenic mice expressing hACE2 from high-titer intranasal SARS-CoV-2 challenge (10 ⁵ plaque forming units). Another antibody, VH ab5 did not compete with hACE2 and ab1, and did not neutralize SARS-CoV-2 although its affinity was comparable to that of ab1. The ab1 sequence has relatively low number of somatic mutations indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 does not have developability liabilities, and thus has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 days) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.