Cross-neutralization of SARS-CoV-2 Kappa and Delta variants by inactivated vaccine-elicited serum and monoclonal antibodies

The SARS-CoV-2 variant of B.1.617 lineage was first identified in India in October 2020, and rapidly spread to many other countries around the world. The variant includes three main sub-lineages, B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.617.3 1 . In light of their high transmissibility, the Kappa and Delta variants had been designated as a variant of interest and a variant of concern by the World Health Organization, respectively. As shown in Fig. 1a , the two variants shared L452R mutation in the receptor-binding domain (RBD). In addition, the variants also harbor unique mutations: E484Q in the Kappa variant and T478K in the Delta variant 2 . Fig. 1: Neutralization of SARS-CoV-2 Kappa and Delta variants by inactivated vaccine-elicited serum and monoclonal antibodies. a Mutations located in the viral spike proteins were identified in the Kappa and Delta variants. Shared mutations in both were highlighted in red, unique mutations in Kappa were marked in green, and mutations in Delta were in blue. b Overall structure of ACE2 in complex with SARS-CoV-2 RBD (left) and footprint of ACE2 on the RBD (right). Three mutation residues (L452, T478, and E484) were shown in red on the RBD. c Structural depiction of ACE2 and representative nAbs from each class binding to the RBD. Class 1: P2C-1F11, REGN10933, CB6; Class 2: BD-368-2, C144, P2B-2F6; Class 3: S309, C110, REGN10987; Class 4: EY6A, S304, H014. d Footprints of four classes of representative nAbs on the RBD. Three mutation residues (L452, T478, and E484) were shown in red on the RBD. e Changes in serum neutralizing titers of inactivated vaccine recipients against Kappa and Delta, as well as L452R, T478K, and E484Q variants, compared with WT. GMTs in ID 50 values were calculated and shown above each variant. ** P < 0.01, *** P < 0.001, **** P < 0.0001. f Competition ELISA (left) and predicted recognizing epitopes (right) of tested monoclonal nAbs binding to RBD with four representative nAbs. The values of competition measured in the highest concentration (10 μg/mL) over 50% were highlighted in light red. g The fold change in IC 50 values of each monoclonal nAbs against mutant and WT viruses. h The fold change in affinity values in binding capacities of each nAb to mutant and WT RBD proteins. Data shown in e – h were means of two or three independent experiments. The changes shown in g , h between 3-fold and 5-fold were marked in green, between 5-fold and 10-fold were in orange. Below the limit of detection (BLD) in red indicated that the inhibition of nAbs was < 50% even in the highest concentration (50 μg/mL), and changes in affinities more than 10-fold were also highlighted in red. Symbol ‘+’ indicates increased neutralization or affinity, and ‘–’ indicates decreased neutralization or affinity. Full size image