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Basic Characteristics of Mutations
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Mutation Site
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R346K |
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Mutation Site Sentence
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Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. |
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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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RBD |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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BA.1.1 |
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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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-
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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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- |
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Literature Information
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PMID
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35662412
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Title
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Potent cross-reactive antibodies following Omicron breakthrough in vaccinees
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Author
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Nutalai R,Zhou D,Tuekprakhon A,Ginn HM,Supasa P,Liu C,Huo J,Mentzer AJ,Duyvesteyn HME,Dijokaite-Guraliuc A,Skelly D,Ritter TG,Amini A,Bibi S,Adele S,Johnson SA,Constantinides B,Webster H,Temperton N,Klenerman P,Barnes E,Dunachie SJ,Crook D,Pollard AJ,Lambe T,Goulder P,Paterson NG,Williams MA,Hall DR,Mongkolsapaya J,Fry EE,Dejnirattisai W,Ren J,Stuart DI,Screaton GR
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Journal
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Cell
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Journal Info
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2022 Jun 9;185(12):2116-2131
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Abstract
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Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.
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Sequence Data
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-
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