Fig. 3: Serum cross-neutralization of infections with SARS-related betacoronaviruses induced by RBD–scNP.
From: Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses
a, Serum neutralization ID50 titres from macaques immunized twice with RBD–scNP, S-2P mRNA-LNP or RBD mRNA-LNP for SARS-CoV, SARS-CoV-2 and SARS-related bat coronaviruses (WIV-1 and SHC014) infections. Symbols indicate individual macaques; black bars show the group geometric mean. Two-tailed exact Wilcoxon test, n = 5 or 8 macaques. b, Serum cross-neutralization ID50 titres before (grey), or after two (light blue) or three (blue), RBD–scNP immunizations. Bars represent the group geometric mean. c, Binding titre (log(AUC)), based on ELISA for the spike protein of human, bat (RaTG13 and SHC014) and pangolin (GXP4L) SARS-related betacoronaviruses, for plasma IgG from macaques immunized twice with RBD–scNP. ECD, ectodomain; S, spike. d, Structural comparison of the epitopes of SARS-CoV-2-specific neutralizing RBD antibody (DH1041) (red) (PDB 7LAA) and cross-neutralizing RBD antibody (DH1047) (magenta) (PDB 7LD1). Left, cartoon view of spike (green), RBD (grey) and receptor binding motif (RBM) (blue). Right, overlay of the RBDs of the two complexes from their respective cryo-electron microscopy structures. e, RBD coloured by conservation within group-2b betacoronaviruses. DH1047 epitope is shown in magenta outline. f, RBD sequence conservation. Heat map displaying pairwise amino acid sequence similarity for 57 representative betacoronaviruses. g, h, Plasma or serum antibody blocking of S-2P binding to ACE2 (grey) and DH1047 (navy blue). g, Plasma antibody inhibition of spike binding. SARS-CoV-2 S-2P (left) or SHC014 S-2P (right) blocking kinetics by serum from macaques immunized twice with RBD–scNP. Group mean ± s.e.m. is shown. n = 5 macaques. Arrows, time of immunization. h, Blocking of SARS-CoV-2 S-2P binding to ACE2 (left) or DH1047 (right). Blocking activity by serum from macaques immunized twice with RBD–scNP or S-2P mRNA-LNP, and humans immunized twice with Pfizer BNT162b2 (BNT162b) or naturally infected with SARS-CoV-2 (convalescent). Each symbol represents an individual and filled bars indicate the group mean in h. Positivity threshold (dashed line) is greater than 20% in h.
