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Human Neutralizing Antibodies to Cold Linear Epitopes and Subdomain 1 of the Sars-Cov-2 Spike Glycoprotein Publisher Pubmed



Bianchini F1 ; Crivelli V1 ; Abernathy ME2 ; Guerra C1 ; Palus M3, 4 ; Muri J1 ; Marcotte H5 ; Piralla A6 ; Pedotti M1 ; De Gasparo R1 ; Simonelli L1 ; Matkovic M1 ; Toscano C1 ; Biggiogero M7 Show All Authors
Authors
  1. Bianchini F1
  2. Crivelli V1
  3. Abernathy ME2
  4. Guerra C1
  5. Palus M3, 4
  6. Muri J1
  7. Marcotte H5
  8. Piralla A6
  9. Pedotti M1
  10. De Gasparo R1
  11. Simonelli L1
  12. Matkovic M1
  13. Toscano C1
  14. Biggiogero M7
  15. Calvaruso V7
  16. Svoboda P3, 4, 8, 9
  17. Rincon TC1
  18. Fava T1
  19. Podesvova L1
  20. Shanbhag AA1
  21. Celoria A1
  22. Sgrignani J1
  23. Stefanik M4, 10
  24. Honig V3, 4
  25. Pranclova V3, 11
  26. Michalcikova T12
  27. Prochazka J12
  28. Guerrini G13
  29. Mehn D13
  30. Ciabattini A14
  31. Abolhassani H5, 15
  32. Jarrossay D1
  33. Uguccioni M1
  34. Medaglini D14
  35. Panhammarstrom Q5
  36. Calzolai L13
  37. Fernandez D16
  38. Baldanti F6, 17
  39. Franzettipellanda A7
  40. Garzoni C18
  41. Sedlacek R12
  42. Ruzek D3, 4, 8
  43. Varani L1
  44. Cavalli A1, 19
  45. Barnes CO2, 20
  46. Robbiani DF1
Show Affiliations
Authors Affiliations
  1. 1. Institute for Research in Biomedicine, Universita della Svizzera italiana, Bellinzona, Switzerland
  2. 2. Department of Biology, Stanford University, Stanford, CA, United States
  3. 3. Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Republic
  4. 4. Veterinary Research Institute, Brno, Czech Republic
  5. 5. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
  6. 6. Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  7. 7. Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland
  8. 8. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
  9. 9. Department of Pharmacology and Pharmacy, Faculty of Veterinary Medicine, University of Veterinary Sciences, Brno, Czech Republic
  10. 10. Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
  11. 11. Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic
  12. 12. Czech Centre of Phenogenomics, Institute of Molecular Genetics, The Czech Academy of Sciences, Vestec, Czech Republic
  13. 13. European Commission, Joint Research Centre (JRC), Ispra, Italy
  14. 14. Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
  15. 15. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  16. 16. Sarafan ChEM-H Macromolecular Structure Knowledge Center, Stanford University, Stanford, CA, United States
  17. 17. Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
  18. 18. Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, Switzerland
  19. 19. Swiss Institute of Bioinformatics, Lausanne, Switzerland
  20. 20. Chan Zuckerberg Biohub, San Francisco, CA, United States

Source: Science Immunology Published:2023


Abstract

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2′ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants. Copyright © 2023 The Authors, some rights reserved.
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