Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection

Figures

• 

  Fig. 1. Isolation of antibodies with cross-activity against SARS-CoV-2 and SARS-CoV. a The clinical profiles of the three SARS-CoV-2 convalescent donors. b The gene usage and CDR sequences of the cloned mAbs exhibiting cross-activity against both SARS-CoV-2 and SARS-CoV. c Binding of the indicated mAbs to S, S1, S2, RBD, NTD of SARS-CoV-2 and S, RBD of SARS-CoV, as measured by ELISA. Data represented means ± SEM. d Binding affinity of the indicated mAbs to SARS-CoV-2 WT RBD, XBB.1.16 RBD, and SARS-CoV RBD was analyzed by BLI. N.B. no binding, N.A. not applicable, binding too weak to accurately calculate.

• 

  Fig. 2. Broad-spectrum neutralizing activity of the mAbs against SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses. a Phylogenetic tree of the tested comprehensive panel of pseudotyped viruses, including SARS-CoV-2 variants, SARS-CoV, and their related sarbecoviruses, as well as MERS-CoV. b Matrix of mutations on S protein across SARS-CoV-2 variants. c Neutralization IC50 values of the six indicated mAbs against the comprehensive panel of pseudotyped viruses.

• 

  Fig. 3. Cryo-EM structure of Omicron XBB.1.16 S trimer in complex with CYFN1006-1. a Cryo-EM structure of the XBB.1.16 S trimer in complex with CYFN1006-1 IgG, shown in surface. b Structure of XBB.1.16 RBD-CYFN1006-1. The RBD is displayed in orange surface mode. The heavy chain and light chain of CYFN1006-1 are shown as ribbons colored in sea green and green yellow, respectively. ACE2 binding epitopes are shown in yellow. c Superimposition of RBD-CYFN1006-1 with RBD-ACE2 (PDB: 7XAZ) reveals the relative position of ACE2 and CYFN1006-1. d Top view of S trimer complexed with CYFN1006-1s, showing that RBDs interact with the neighboring CYFN1006-1. The RBD and CYFN1006-1 residues involved in the interactions are colored green and red, respectively. e Detailed interactions between the CYFN1006-1 and XBB.1.16 RBD. Hydrogen bonds are represented by dashed lines. Hydrophobic interactions are marked with red circles.

• 

  Fig. 4. Cryo-EM structure Omicron EG.5.1 S trimer in complex with CYFN1006-2. a Cryo-EM structures of the EG.5.1 S trimer in complex with the CYFN1006-2 IgG, shown on the surface. b Structure of EG.5.1 RBD-CYFN1006-2. The RBD is displayed in orange surface mode. The heavy chain and light chain of CYFN1006-2 are shown as ribbons colored in dodger blue and cyan, respectively. ACE2 binding epitopes are shown in yellow. c Superimposition of RBD-CYFN1006-2 with RBD-ACE2 (PDB: 7XAZ) revealed the relative position of ACE2 and CYFN1006-2. d Top view of S trimer complexed with CYFN1006-2s, showing that RBDs interact with the neighboring CYFN1006-2. The RBD and CYFN1006-2 residues involved in the interactions are colored green and red, respectively. e Detailed interactions between the CYFN1006-2 and EG.5.1 RBD. Hydrogen bonds are represented by dashed lines. Hydrophobic interactions are marked with red circles.

• 

  Fig. 5. Prophylactic efficacy of CYFN1006-1 against SARS-CoV-2 JN.1 in hamsters. a Schematic of the in vivo mAb efficacy test experiments in hamsters. 6-to-8-week-old male Syrian golden hamsters were treated with one dose of mAb CYFN1006-1 antibody (20 mg/kg, n = 5) through intraperitoneal injection antibodies at 8 h before challenging with 1 × 104 PFU JN.1. Animals were euthanized at 4 dpi for collection of nasal turbinates (NT) and lung tissues for detection of viral burden and viral antigen expression. b, c Hamster NT and lungs viral sgE copies and infectious titers were measured with (b) probe-specific RT-qPCR and (c) TCID50 assay. d SARS-CoV-2-N protein in hamster lung tissue was stained with anti-SARS-CoV-2-N antibody and visualized using fluorescent microscopy, with DAPI staining used for cell nuclei. Scale bar, 200 μm. e Histological examination of hamster lungs with hematoxylin and eosin (H&E) staining. Scale bar, 200 μm. Data represented means ± SEM from the indicated number of biological repeats. p Values were determined by unpaired t-test.