Details

Autor(en) / Beteiligte

• Zhang, Fengwen
• Jenkins, Jesse
• de Carvalho, Renan V H
• Nakandakari-Higa, Sandra
• Chen, Teresia
• Abernathy, Morgan E
• Baharani, Viren A
• Nyakatura, Elisabeth K
• Andrew, David
• Lebedeva, Irina V
• Lorenz, Ivo C
• Hoffmann, H-Heinrich
• Rice, Charles M
• Victora, Gabriel D
• Barnes, Christopher O
• Hatziioannou, Theodora
• Bieniasz, Paul D

Titel

Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies

Ist Teil von

• Nature microbiology, 2023-06, Vol.8 (6), p.1051-1063

Ort / Verlag

England

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 . 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.