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Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.
Pymm, Phillip; Adair, Amy; Chan, Li-Jin; Cooney, James P; Mordant, Francesca L; Allison, Cody C; Lopez, Ester; Haycroft, Ebene R; O'Neill, Matthew T; Tan, Li Lynn; Dietrich, Melanie H; Drew, Damien; Doerflinger, Marcel; Dengler, Michael A; Scott, Nichollas E; Wheatley, Adam K; Gherardin, Nicholas A; Venugopal, Hariprasad; Cromer, Deborah; Davenport, Miles P; Pickering, Raelene; Godfrey, Dale I; Purcell, Damian F J; Kent, Stephen J; Chung, Amy W; Subbarao, Kanta; Pellegrini, Marc; Glukhova, Alisa; Tham, Wai-Hong.
  • Pymm P; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Adair A; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Chan LJ; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Cooney JP; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Mordant FL; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Allison CC; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Lopez E; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Haycroft ER; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • O'Neill MT; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Tan LL; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Dietrich MH; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Drew D; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Doerflinger M; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Dengler MA; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Scott NE; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Wheatley AK; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Gherardin NA; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Venugopal H; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Cromer D; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Davenport MP; Infectious Diseases and Immune Defences Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Pickering R; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Godfrey DI; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Purcell DFJ; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Kent SJ; Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Chung AW; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Subbarao K; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Pellegrini M; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
  • Glukhova A; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
  • Tham WH; Department of Mathematics and Statistics, University of New South Wales, Sydney, NSW 2052, Australia.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1203483
Semantic information from SemMedBD (by NLM)
1. Antibodie AFFECTS C0020964
Subject
Antibodie
Predicate
AFFECTS
Object
C0020964
2. Therapeutic procedure METHOD_OF Prophylactic treatment
Subject
Therapeutic procedure
Predicate
METHOD_OF
Object
Prophylactic treatment
3. Vicugna pacos LOCATION_OF VHH Immunoglobulin Fragments
Subject
Vicugna pacos
Predicate
LOCATION_OF
Object
VHH Immunoglobulin Fragments
4. VHH Immunoglobulin Fragments AFFECTS Engaged to be married
Subject
VHH Immunoglobulin Fragments
Predicate
AFFECTS
Object
Engaged to be married
5. Engaged to be married PROCESS_OF human group
Subject
Engaged to be married
Predicate
PROCESS_OF
Object
human group
6. Prophylactic treatment TREATS Mus
Subject
Prophylactic treatment
Predicate
TREATS
Object
Mus
7. Antibodies, Neutralizing AFFECTS Immune response
Subject
Antibodies, Neutralizing
Predicate
AFFECTS
Object
Immune response
8. Therapeutic procedure METHOD_OF Prophylactic treatment
Subject
Therapeutic procedure
Predicate
METHOD_OF
Object
Prophylactic treatment
9. Vicugna pacos LOCATION_OF VHH Immunoglobulin Fragments
Subject
Vicugna pacos
Predicate
LOCATION_OF
Object
VHH Immunoglobulin Fragments
10. VHH Immunoglobulin Fragments AFFECTS Engaged to be married
Subject
VHH Immunoglobulin Fragments
Predicate
AFFECTS
Object
Engaged to be married
11. Engaged to be married PROCESS_OF human group
Subject
Engaged to be married
Predicate
PROCESS_OF
Object
human group
12. Prophylactic treatment TREATS Mus
Subject
Prophylactic treatment
Predicate
TREATS
Object
Mus
ABSTRACT
Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 104-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Single-Domain Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Viral Topics: Variants Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2101918118

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Single-Domain Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Viral Topics: Variants Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2101918118