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19 Apr 2022
DOI: 10.1126/scitranslmed.abn6859
LIHONG LIU, SHO IKETANI, YICHENG GUO, XESWAR R. REDDEM, RYAN G. CASNER, MANOJ S. NAIR, JIAN YU, JASPER F.-W. CHAN, MAPLE WANG[...]DAVID D. HO +22 authors
Comparative antibody analysis
Antibodies that broadly neutralize SARS-CoV-2 and other sarbecoviruses are essential for the global response to the ongoing COVID-19 pandemic. Here, Liu et al. identified a human monoclonal antibody, 10-40, isolated from an individual with a prior SARS-CoV-2 infection, that could broadly neutralize several variants of SARS-CoV-2, SARS-CoV, and other coronaviruses. 10-40 and other antibodies targeting a similar epitope shared a common heavy-chain complementarity-determining region 3 (CDRH3) motif, suggesting that this class of antibodies may be important to elicit for effective pan-sarbecovirus vaccines.
Abstract
The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)–directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.
DOI: 10.1126/scitranslmed.abn6859
LIHONG LIU, SHO IKETANI, YICHENG GUO, XESWAR R. REDDEM, RYAN G. CASNER, MANOJ S. NAIR, JIAN YU, JASPER F.-W. CHAN, MAPLE WANG[...]DAVID D. HO +22 authors
Comparative antibody analysis
Antibodies that broadly neutralize SARS-CoV-2 and other sarbecoviruses are essential for the global response to the ongoing COVID-19 pandemic. Here, Liu et al. identified a human monoclonal antibody, 10-40, isolated from an individual with a prior SARS-CoV-2 infection, that could broadly neutralize several variants of SARS-CoV-2, SARS-CoV, and other coronaviruses. 10-40 and other antibodies targeting a similar epitope shared a common heavy-chain complementarity-determining region 3 (CDRH3) motif, suggesting that this class of antibodies may be important to elicit for effective pan-sarbecovirus vaccines.
Abstract
The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)–directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.
