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Basic Characteristics of Mutations
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Mutation Site
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K417N |
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Mutation Site Sentence
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Particularly, Omi-18 contains F27I, S53A, and Y58F (Figure S8), and structural analysis revealed that these SHMs generate new interactions with the RBD and are capable of adapting K417N substitution (Figure S9), explaining its broad neutralization by K417N bearing Omicron subvariants. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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Standardized Encoding Gene
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Genotype/Subtype
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Omicron |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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Guangzhou(China) |
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Literature Information
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PMID
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38044868
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Title
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Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents
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Author
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Yan Q,Zhang Y,Hou R,Pan W,Liang H,Gao X,Deng W,Huang X,Qu L,Tang C,He P,Liu B,Wang Q,Zhao X,Lin Z,Chen Z,Li P,Han J,Xiong X,Zhao J,Li S,Niu X,Chen L
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Journal
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Emerging microbes & infections
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Journal Info
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2024 Dec;13(1):2290841
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Abstract
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Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naive individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naive B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naive B cell repertoires, providing a valuable reference for future vaccine design and evaluation.
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Sequence Data
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-
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