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Basic Characteristics of Mutations
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Mutation Site
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K403R |
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Mutation Site Sentence
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We previously reported that pseudovirus infectivity of Vero cells was significantly perturbed in Deltains16MPLF, K403R, D450N, Q493R, and S621P. |
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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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BA.2.86 |
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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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Cell line
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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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39827186
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Title
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Reverse mutational scanning of SARS-CoV-2 spike BA.2.86 identifies epitopes contributing to immune escape from polyclonal sera
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Author
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Bdeir N,Luddecke T,Maass H,Schmelz S,Rand U,Jacobsen H,Metzdorf K,Kulkarni U,Cossmann A,Stankov MV,Hoffmann M,Pohlmann S,Blankenfeldt W,Dopfer-Jablonka A,Behrens GMN,Cicin-Sain L
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Journal
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Nature communications
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Journal Info
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2025 Jan 18;16(1):809
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Abstract
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The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.2. BA.2.86 and its JN.1 derivative evade neutralization by serum antibodies of fully vaccinated individuals. In this study, we elucidate epitopes driving the immune escape of BA.2.86 and JN.1 via pseudovirus neutralization. Here we generate 33 BA.2.86 mutants, each reverting a single mutation back to BA.2. We use this library in an approach that we call reverse mutational scanning to define distinct neutralization titers against each epitope. Mutations within the receptor binding domain at K356T, V483Delta, and to a lesser extent N460K, A484K, and F486P enhance immune escape. Interestingly, 16insMPLF within the spike N-terminal domain and P621S within S1/S2 also significantly contribute to antibody escape of BA.2.86. Upon XBB.1.5 booster vaccination, neutralization titers against JN.1 and BA.2.86 improve considerably, and residual immune escape is driven by 16insMPLF, N460K, E554K, and to a lesser extent P621S, and A484K.
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Sequence Data
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-
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