Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

Autor: Nicholas C. Wu, Xueyong Zhu, Marit J. van Gils, Jakob Kreye, Chang-Chun D Lee, Linghang Peng, Hejun Liu, Meng Yuan, Abigail M. Jackson, Dennis R. Burton, Andrew B. Ward, Rogier W. Sanders, David Nemazee, S. Momsen Reincke, Harald Prüss, Ian A. Wilson, Deli Huang
Přispěvatelé: Medical Microbiology and Infection Prevention, AII - Infectious diseases
Jazyk: angličtina
Rok vydání: 2021
Předmět:
virology [COVID-19]
medicine.disease_cause
Antibodies
Viral
metabolism [Angiotensin-Converting Enzyme 2]
genetics [Spike Glycoprotein
Coronavirus]
Neutralization
Germline
Epitopes
genetics [Antigens
Viral]
immunology [SARS-CoV-2]
immunology [COVID-19]
Antigens
Viral
Coronavirus
chemistry.chemical_classification
Mutation
Multidisciplinary
Microbio
genetics [SARS-CoV-2]
spike protein
SARS-CoV-2
Antigenic Variation
Vaccination
Spike Glycoprotein
Coronavirus
chemistry [Antigens
Viral]
ddc:500
Angiotensin-Converting Enzyme 2
Antibody
chemistry [SARS-CoV-2]
Protein Binding
chemistry [Spike Glycoprotein
Coronavirus]
Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
ACE2 protein
human
metabolism [Antibodies
Neutralizing]
Biology
Receptor binding site
Article
Antigenic drift
immunology [Antibodies
Viral]
Protein Domains
Report
medicine
Humans
metabolism [Receptors
Coronavirus]
Gene
Immune Evasion
Binding Sites
metabolism [Antibodies
Viral]
immunology [Spike Glycoprotein
Coronavirus]
SARS-CoV-2
Biochem
COVID-19
Virology
immunology [Antigens
Viral]
Antibodies
Neutralizing
immunology [Antibodies
Neutralizing]
metabolism [Antigens
Viral]
Enzyme
chemistry
metabolism [Spike Glycoprotein
Coronavirus]
biology.protein
Binding Sites
Antibody
Reports
Receptors
Coronavirus
Zdroj: Science 373(6556), 818-823 (2021). doi:10.1126/science.abh1139
bioRxiv
article-version (status) pre
article-version (number) 1
Science, 373(6556), 818-823. American Association for the Advancement of Science
Science (New York, N.y.)
ISSN: 0036-8075
Popis: 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.
Databáze: OpenAIRE
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