The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice

  1. Rafael Bayarri-Olmos
  2. Laust Bruun Johnsen
  3. Manja Idorn
  4. Line S Reinert
  5. Anne Rosbjerg
  6. Søren Vang
  7. Cecilie Bo Hansen
  8. Charlotte Helgstrand
  9. Jais Rose Bjelke
  10. Theresa Bak-Thomsen
  11. Søren R Paludan
  12. Peter Garred
  13. Mikkel-Ole Skjoedt  Is a corresponding author
  1. Recombinant Protein and Antibody Laboratory, Copenhagen University Hospital, Denmark
  2. Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet Copenhagen University Hospital, Denmark
  3. Novo Nordisk A/S, Denmark
  4. Department of Biomedicine, Aarhus University, Denmark
  5. Institute of Immunology and Microbiology, University of Copenhagen, Denmark
  6. Department of Molecular Medicine, Aarhus University Hospital, Denmark
6 figures and 1 additional file

Figures

Biophysical characterization of recombinant receptor-binding domain (RBD) variants.

(A) Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) total protein stain of RBD variants and angiotensin-converting enzyme-2 (ACE-2). (B) Size-exclusion chromatography (SEC) …

Development of COVID-19-like disease in mice.

(A) Weight evolution of K18-hACE2 mice challenged intranasally with 2.5 × 103 (low, n = 9 per group) or 2.5 × 104 p.f.u. (high, n = 5 per group) SARS-CoV-2 B.1 (Freiburg isolate, FR-4286) or …

Antibody-mediated inhibition potency of recovered COVID-19 patient sera.

(A) Inhibition of wild-type (wt), N439K, and N501Y receptor-binding domain (RBD) towards angiotensin-converting enzyme-2 (ACE-2) in serum from convalescent COVID-19 individuals (n = 140). Friedman …

Antibody-mediated inhibition potency of polyclonal sera and monoclonal antibodies (mAbs) isolated from mice immunized against wild-type (wt) receptor-binding domain (RBD) or spike protein.

IC50 comparison of the inhibition of polyclonal mice sera from an animal vaccine model based on RBD (A) or spike (B) challenged with RBD wt, N439K, and N501Y. Connecting lines represent non-linear …

Author response image 1
Inhibitory potency of COVID-19 convalescent patient sera against RBD variants.

Antibody-mediated inhibition of serum from recovered COVID-19 patients (n = 150) against RBD wt, N501Y and P.1 (harboring the Y417N, E484K, and N501Y mutations). Statistical comparisons between …

Author response image 2

Additional files

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