Your browser doesn't support javascript.
Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability.
Burnett, Deborah L; Jackson, Katherine J L; Langley, David B; Aggrawal, Anupria; Stella, Alberto Ospina; Johansen, Matt D; Balachandran, Harikrishnan; Lenthall, Helen; Rouet, Romain; Walker, Gregory; Saunders, Bernadette M; Singh, Mandeep; Li, Hui; Henry, Jake Y; Jackson, Jennifer; Stewart, Alastair G; Witthauer, Franka; Spence, Matthew A; Hansbro, Nicole G; Jackson, Colin; Schofield, Peter; Milthorpe, Claire; Martinello, Marianne; Schulz, Sebastian R; Roth, Edith; Kelleher, Anthony; Emery, Sean; Britton, Warwick J; Rawlinson, William D; Karl, Rudolfo; Schäfer, Simon; Winkler, Thomas H; Brink, Robert; Bull, Rowena A; Hansbro, Philip M; Jäck, Hans-Martin; Turville, Stuart; Christ, Daniel; Goodnow, Christopher C.
  • Burnett DL; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia. Electronic address: d.burnett@garvan.org.au.
  • Jackson KJL; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Langley DB; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Aggrawal A; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Stella AO; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Johansen MD; Center for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
  • Balachandran H; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Lenthall H; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Rouet R; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
  • Walker G; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
  • Saunders BM; Center for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
  • Singh M; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
  • Li H; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Henry JY; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Jackson J; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Stewart AG; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia.
  • Witthauer F; Division of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
  • Spence MA; Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
  • Hansbro NG; Center for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
  • Jackson C; Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
  • Schofield P; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
  • Milthorpe C; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Martinello M; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Schulz SR; Division of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
  • Roth E; Division of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
  • Kelleher A; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Emery S; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Britton WJ; Centenary Institute, The University of Sydney, Sydney, NSW 2006, Australia.
  • Rawlinson WD; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Serology and Virology Division (SAViD), NSW Health Pathology, SEALS Randwick, Sydney, NSW 2031, Australia.
  • Karl R; Division of Genetics, Department Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
  • Schäfer S; Division of Genetics, Department Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
  • Winkler TH; Division of Genetics, Department Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
  • Brink R; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
  • Bull RA; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Hansbro PM; Center for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
  • Jäck HM; Division of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
  • Turville S; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
  • Christ D; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
  • Goodnow CC; Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Cellular Genomics Futures Institute, UNSW Sydney, Sydney, NSW 2052, Australia.
Immunity ; 54(12): 2908-2921.e6, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1521063
ABSTRACT
Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies.
Subject(s)
Keywords
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Severe acute respiratory syndrome-related coronavirus / Spike Glycoprotein, Coronavirus / Betacoronavirus / COVID-19 Vaccines Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article

Similar

MEDLINE
LILACS
LIS
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Severe acute respiratory syndrome-related coronavirus / Spike Glycoprotein, Coronavirus / Betacoronavirus / COVID-19 Vaccines Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article