Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

By T. Rogers, Fangzhu Zhao, Deli Huang, N. Beutler, Alison Burns, Wan-ting He, Oliver Limbo, Chloe Smith, G. Song, J. Woehl and 24 more. Science, 2020

1,300 citations recorded by the source corpus.

Protective neutralizing antibodies Antibodies produced by survivors of coronavirus disease 2019 (COVID-19) may be leveraged to develop therapies. A first step is identifying neutralizing antibodies, which confer strong protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rogers et al. used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors. Antibodies were selected for binding to the viral spike protein, which facilitates entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Most isolated antibodies bound to regions of the spike outside of the receptor binding domain (RBD); however, a larger proportion of the RBD-binding antibodies were neutralizing, with the most potent binding at a site that overlaps the ACE2 binding site. Two of the neutralizing antibodies were tested in Syrian hamsters and provided protection against SARS-CoV-2 infection. Science, this issue p. 956 Passive transfer of a neutralizing antibody provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. 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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/bb3621a8d4d1d25557aa98e23f44903a9c6c3a07

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In Infectious Diseases

Citations in the corpus

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection (2021, background): “1, C and D), as RBD is the target of most neutralizing antibodies against SARS-CoV-2 (4, 27, 46, 47).”
Efficient evolution of human antibodies from general protein language models (2023, neutral): “Production of this cell line is described in detail by Rogers et al. 65 with the addition of stable TMPRSS2 incorporation.”
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity (2020, neutral): “The RBD domain is the primary target of SARS-CoV-2-neutralizing antibodies (Ju et al., 2020; Rogers et al., 2020), much like what was found for SARS-CoV (Subbarao, 2020).”
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, neutral): “…reports have described the isolation of mAbs from SARS-CoV-2-infected individuals, and a few of them were characterized structurally (Barnes et al., 2020; Baum et al., 2020; Brouwer et al., 2020; Chi et al., 2020; Rogers et al., 2020; Seydoux et al., 2020; Wang et al., 2020a; Wu et al., 2020).”
Animal models for COVID-19 (2020, background): “Adoptive transfer of SARS-CoV-2 neutralizing antibodies protected hamsters from SARS-CoV-2-induced disease 43 .”