Shared N417-Dependent Epitope on the SARS-CoV-2 Omicron, Beta, and Delta Plus Variants
Thandeka Moyo-Gwete, Mashudu Madzivhandila, Nonhlanhla N. Mkhize, Prudence Kgagudi, Frances Ayres, Bronwen E. Lambson, Nelia P. Manamela, Simone I. Richardson, Zanele Makhado, Mieke A. van der Mescht, Zelda de Beer, Talita Roma de Villiers, Wendy A. Burgers, Ntobeko Ntusi, Theresa M. Rossouw, Veronica Ueckermann, Michael T. Boswell, Penny L. Moore
Abstract
The evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring various immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants and to define shared epitopes. We show that Beta and Delta infections resulted in antibody responses that were more cross-reactive than the original D614G variant, but they had differing patterns of cross-reactivity. We further isolated an antibody from Beta infection which targeted the N417 site, enabling cross-neutralization of Beta, Delta+, and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics.