@techreport{c23889e3ff0d4c5e9526d2514559e21e,
title = "Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants",
abstract = "The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.Competing Interest StatementRelated to this work, the German Center for Neurodegenerative Diseases (DZNE) and Charite - Universitatsmedizin Berlin have filed a patent application that included the anti-SARS-CoV-2 antibody CV05-163.",
keywords = "Coronavirus, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Novel coronavirus, 2019-nCoV, Pandemic",
author = "Meng Yuan and Deli Huang and Lee, {Chang-Chun D.} and Wu, {Nicholas C.} and Jackson, {Abigail M.} and Xueyong Zhu and Hejun Liu and Linghang Peng and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and Burton, {Dennis R.} and Reincke, {S. Momsen} and Harald Pr{\"u}ss and Jakob Kreye and David Nemazee and Ward, {Andrew B.} and Wilson, {Ian A.}",
year = "2021",
month = feb,
day = "17",
doi = "10.1101/2021.02.16.430500",
language = "English (US)",
series = "bioRxiv",
publisher = "Cold Spring Harbor Laboratory Press",
address = "United States",
type = "WorkingPaper",
institution = "Cold Spring Harbor Laboratory Press",
}