Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
SUMMARY The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb1, retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974, neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
Gori Andrea、Riva Agostino、Piccoli Luca、Havenar-Daughton Colin、Yin Li、Franko Nicholas M.、Logue Jenni、Cipp¨¤ Pietro、Franzetti-Pellanda Alessandra、Garzoni Christian、Halfmann Peter J.、Hebner Christy、Cameroni Elisabetta、Bowen John E.、Zatta Fabrizia、Noack Julia、Farhat Nisar、Sprouse Kaitlin R.、Ceschi Alessandro、Purcell Lisa A.、Pizzuto Matteo Samuele、Diamond Michael S.、Veesler David、Snell Gyorgy、Corti Davide、Ferrari Paolo、Kawaoka Yoshihiro、Rosen Laura E.、Saliba Christian、Kaiser Hannah、Grifantini Renata、Giannini Olivier、Chu Helen、Virgin Herbert W.、Chen Alex、Pinto Dora、Bassi Jessica、Culap Katja、Walls Alexandra C.、Gustafsson Claes、VanBlargan Laura A.、Iulio Julia di、Soriaga Leah、Lanzavecchia Antonio、Mazzitelli Ignacio、Silacci-Fregni Chiara、De Marco Anna、Dillen Josh R.、Sun David、Maher Cyrus、Iqbal Najeeha Talat、Czudnochowski Nadine、Zepeda Samantha K.、Telenti Amalio、Geffner Jorge、Powell Abigail E.
Infectious Disease Unit, Fondazione IRCCS Ca?ˉ GrandaDepartment of Biomedical and Clinical Sciences ??L.Sacco?ˉ (DIBIC), Universit¨¤ di MilanoHumabs Biomed SA, a subsidiary of Vir BiotechnologyVir BiotechnologyVir BiotechnologyDivision of Allergy and Infectious Diseases, University of WashingtonDivision of Allergy and Infectious Diseases, University of WashingtonFaculty of Biomedical Sciences, Universit¨¤ della Svizzera italiana||Department of Clinical Pharmacology and Toxicology, University Hospital Zurich||Faculty of Medicine, University of ZurichClinical Research Unit, Clinica Luganese MoncuccoClinic of Internal Medicine and Infectious Diseases, Clinica Luganese MoncuccoInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-MadisonVir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyDepartment of Biochemistry, University of WashingtonHumabs Biomed SA, a subsidiary of Vir BiotechnologyVir BiotechnologyVir BiotechnologyDepartment of Biochemistry, University of WashingtonFaculty of Biomedical Sciences, Universit¨¤ della Svizzera italiana||Clinical Trial Unit, Ente Ospedaliero Cantonale||Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Science of Southern Switzerland, Ente Ospedaliero Cantonale||Department of Clinical Pharmacology and Toxicology, University Hospital ZurichVir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyDepartment of Medicine, Washington University of School of Medicine||Department of Pathology and Immunology, Washington University School of Medicine||Department of Molecular Microbiology, Washington University School of MedicineDepartment of Biochemistry, University of Washington||Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese MoncuccoVir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyFaculty of Biomedical Sciences, Universit¨¤ della Svizzera italiana||Division of Nephrology, Ente Ospedaliero Cantonale||Faculty of Medicine, University of ZurichInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison||Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo||The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research InstituteVir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyVir BiotechnologyNational Institute of Molecular GeneticsFaculty of Biomedical Sciences, Universit¨¤ della Svizzera italiana||Department of Medicine, Ente Ospedaliero CantonaleDivision of Allergy and Infectious Diseases, University of WashingtonVir Biotechnology||Howard Hughes Medical Institute||Department of Internal Medicine, UT Southwestern Medical CenterVir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyDepartment of Biochemistry, University of Washington||Howard Hughes Medical InstituteATUMDepartment of Medicine, Washington University of School of MedicineVir BiotechnologyVir BiotechnologyHumabs Biomed SA, a subsidiary of Vir Biotechnology||Instituto de Investigaciones Biom¨|dicas en Retrovirus y SIDA (INBIRS), Facultad de MedicinaInstituto de Investigaciones Biom¨|dicas en Retrovirus y SIDA (INBIRS), Facultad de MedicinaHumabs Biomed SA, a subsidiary of Vir BiotechnologyHumabs Biomed SA, a subsidiary of Vir BiotechnologyVir BiotechnologyVir BiotechnologyVir BiotechnologyDepartment of Paediatrics and Child Health, Aga Khan UniversityVir BiotechnologyDepartment of Biochemistry, University of WashingtonDepartment of Biochemistry, University of WashingtonInstituto de Investigaciones Biom¨|dicas en Retrovirus y SIDA (INBIRS), Facultad de MedicinaVir Biotechnology
医药卫生理论医学研究方法生物科学研究方法、生物科学研究技术
SARS-CoV-2COVID-19antibodyvaccineneutralizing antibodiesimmune evasion
Gori Andrea,Riva Agostino,Piccoli Luca,Havenar-Daughton Colin,Yin Li,Franko Nicholas M.,Logue Jenni,Cipp¨¤ Pietro,Franzetti-Pellanda Alessandra,Garzoni Christian,Halfmann Peter J.,Hebner Christy,Cameroni Elisabetta,Bowen John E.,Zatta Fabrizia,Noack Julia,Farhat Nisar,Sprouse Kaitlin R.,Ceschi Alessandro,Purcell Lisa A.,Pizzuto Matteo Samuele,Diamond Michael S.,Veesler David,Snell Gyorgy,Corti Davide,Ferrari Paolo,Kawaoka Yoshihiro,Rosen Laura E.,Saliba Christian,Kaiser Hannah,Grifantini Renata,Giannini Olivier,Chu Helen,Virgin Herbert W.,Chen Alex,Pinto Dora,Bassi Jessica,Culap Katja,Walls Alexandra C.,Gustafsson Claes,VanBlargan Laura A.,Iulio Julia di,Soriaga Leah,Lanzavecchia Antonio,Mazzitelli Ignacio,Silacci-Fregni Chiara,De Marco Anna,Dillen Josh R.,Sun David,Maher Cyrus,Iqbal Najeeha Talat,Czudnochowski Nadine,Zepeda Samantha K.,Telenti Amalio,Geffner Jorge,Powell Abigail E..Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift[EB/OL].(2025-03-28)[2025-06-12].https://www.biorxiv.org/content/10.1101/2021.12.12.472269.点此复制
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