tetano
Editor, Senior Moderator
Nat Microbiol
. 2023 May 15.
doi: 10.1038/s41564-023-01389-9. Online ahead of print. Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies
Fengwen Zhang[SUP] 1 [/SUP], Jesse Jenkins[SUP] 1 [/SUP], Renan V H de Carvalho[SUP] 2 [/SUP], Sandra Nakandakari-Higa[SUP] 2 [/SUP], Teresia Chen[SUP] 3 [/SUP], Morgan E Abernathy[SUP] 3 [/SUP], Viren A Baharani[SUP] 1 [/SUP], Elisabeth K Nyakatura[SUP] 4 [/SUP], David Andrew[SUP] 4 [/SUP], Irina V Lebedeva[SUP] 4 [/SUP], Ivo C Lorenz[SUP] 4 [/SUP], H-Heinrich Hoffmann[SUP] 5 [/SUP], Charles M Rice[SUP] 5 [/SUP], Gabriel D Victora[SUP] 2 [/SUP], Christopher O Barnes[SUP] 3 6 [/SUP], Theodora Hatziioannou[SUP] 7 [/SUP], Paul D Bieniasz[SUP] 8 9 [/SUP]
Affiliations
Human monoclonal antibodies (mAbs) that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been isolated from convalescent individuals and developed into therapeutics for SARS-CoV-2 infection. However, therapeutic mAbs for SARS-CoV-2 have been rendered obsolete by the emergence of mAb-resistant virus variants. Here we report the generation of a set of six human mAbs that bind the human angiotensin-converting enzyme-2 (hACE2) receptor, rather than the SARS-CoV-2 spike protein. We show that these antibodies block infection by all hACE2 binding sarbecoviruses tested, including SARS-CoV-2 ancestral, Delta and Omicron variants at concentrations of ~7-100 ng ml[SUP]-1[/SUP]. These antibodies target an hACE2 epitope that binds to the SARS-CoV-2 spike, but they do not inhibit hACE2 enzymatic activity nor do they induce cell-surface depletion of hACE2. They have favourable pharmacology, protect hACE2 knock-in mice against SARS-CoV-2 infection and should present a high genetic barrier to the acquisition of resistance. These antibodies should be useful prophylactic and treatment agents against any current or future SARS-CoV-2 variants and might be useful to treat infection with any hACE2-binding sarbecoviruses that emerge in the future.
. 2023 May 15.
doi: 10.1038/s41564-023-01389-9. Online ahead of print. Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies
Fengwen Zhang[SUP] 1 [/SUP], Jesse Jenkins[SUP] 1 [/SUP], Renan V H de Carvalho[SUP] 2 [/SUP], Sandra Nakandakari-Higa[SUP] 2 [/SUP], Teresia Chen[SUP] 3 [/SUP], Morgan E Abernathy[SUP] 3 [/SUP], Viren A Baharani[SUP] 1 [/SUP], Elisabeth K Nyakatura[SUP] 4 [/SUP], David Andrew[SUP] 4 [/SUP], Irina V Lebedeva[SUP] 4 [/SUP], Ivo C Lorenz[SUP] 4 [/SUP], H-Heinrich Hoffmann[SUP] 5 [/SUP], Charles M Rice[SUP] 5 [/SUP], Gabriel D Victora[SUP] 2 [/SUP], Christopher O Barnes[SUP] 3 6 [/SUP], Theodora Hatziioannou[SUP] 7 [/SUP], Paul D Bieniasz[SUP] 8 9 [/SUP]
Affiliations
- PMID: 37188812
- DOI: 10.1038/s41564-023-01389-9
Human monoclonal antibodies (mAbs) that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been isolated from convalescent individuals and developed into therapeutics for SARS-CoV-2 infection. However, therapeutic mAbs for SARS-CoV-2 have been rendered obsolete by the emergence of mAb-resistant virus variants. Here we report the generation of a set of six human mAbs that bind the human angiotensin-converting enzyme-2 (hACE2) receptor, rather than the SARS-CoV-2 spike protein. We show that these antibodies block infection by all hACE2 binding sarbecoviruses tested, including SARS-CoV-2 ancestral, Delta and Omicron variants at concentrations of ~7-100 ng ml[SUP]-1[/SUP]. These antibodies target an hACE2 epitope that binds to the SARS-CoV-2 spike, but they do not inhibit hACE2 enzymatic activity nor do they induce cell-surface depletion of hACE2. They have favourable pharmacology, protect hACE2 knock-in mice against SARS-CoV-2 infection and should present a high genetic barrier to the acquisition of resistance. These antibodies should be useful prophylactic and treatment agents against any current or future SARS-CoV-2 variants and might be useful to treat infection with any hACE2-binding sarbecoviruses that emerge in the future.