Shared N417-Dependent Epitope on SARS-CoV-2 variants

31 August 2022

Dr Thandeka Moyo-Gwete and colleagues at the NICD published a study in the Journal of Virology that sought to understand the antibody responses elicited by different SARS-CoV-2 variants and to define shared epitopes. As SARS-CoV-2 variants of concern (VOCs) have arisen, they have shown variable escape from antibody responses and have been shown to trigger qualitatively different antibody responses during infection.

The team at the NICD studied plasma from individuals infected with either the D614G, Beta or Delta variants. Although the Beta and Delta variants elicited antibody responses that were overall more cross-reactive than those triggered by D614G, the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta Plus, which differs from Delta by a single K417N mutation, suggesting that the plasma response targets the N417 residue.

They then isolated monoclonal antibodies from an individual with plasma responses against VOCs which possess the N417 residue. The team isolated a novel, cross-reactive N417-dependent antibody which utilised the IGHV3-23*01 germline gene and had somatic hypermutations similar to those of previously described public antibodies which target the 417 residue. Understanding antibodies targeting escape mutations, such as K417N, may aid in the development of next-generation antibody therapeutics and vaccines.

Cover Photo: Dr Thandeka Moyo-Gwete