Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

• DOI: 10.1016/j.immuni.2021.03.023
• Publication Date: 2021-04-02T02:02:57Z
• Authors: Carl Graham; Jeffrey Seow; Isabella Huettner; Hataf Khan; Neophytos Kouphou; Sam Acors; Helena Winstone; Suzanne Pickering; Rui Pedro Galao; Liane Dupont; Maria Jose Lista; Jose M. Jimenez-G...; Adam G. Laing; Yin Wu; Magdalene Joseph; Luke Muir; Marit J. van Gils; Weng M. Ng; Helen M.E. Duyves...; Yuguang Zhao; Thomas A. Bowden; Manu Shankar-Hari; Annachiara Rosa; Peter Cherepanov; Laura E. McCoy; Adrian C. Hayday; Stuart J.D. Neil; Michael H. Malim; Katie J. Doores
• Keywords: Subdominant; Antigenicity

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with ACE2 on host cells is essential for viral entry. RBD dominant target neutralizing antibodies, and several epitopes have been molecularly characterized. Analysis circulating variants has revealed mutations arising in RBD, N-terminal (NTD) S2 subunits Spike. To understand how these affect antigenicity, we isolated characterized >100 monoclonal antibodies targeting NTD, from SARS-CoV-2-infected individuals. Approximately 45% showed activity, which ∼20% were NTD specific. NTD-specific formed two distinct groups: first was highly potent against infectious virus, whereas second less displayed glycan-dependant neutralization activity. Mutations present B.1.1.7 frequently conferred resistance to antibodies. This work demonstrates that subdominant should be considered when investigating antigenic drift emerging variants.