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Basic Characteristics of Mutations
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Mutation Site
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A774R |
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Mutation Site Sentence
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While rVSV-EBOVA774R was not a complete escape, the activity of A774 against it was ~10-fold reduced (40 nM) in comparison to neutralizing activity against rVSV-EBOV (Fig 5A and 5B). |
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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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GP |
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Standardized Encoding Gene
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GP
|
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Genotype/Subtype
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- |
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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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Y |
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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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Location
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- |
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Literature Information
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PMID
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38603762
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Title
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Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies
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Author
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Wirchnianski AS,Nyakatura EK,Herbert AS,Kuehne AI,Abbasi SA,Florez C,Storm N,McKay LGA,Dailey L,Kuang E,Abelson DM,Wec AZ,Chakraborti S,Holtsberg FW,Shulenin S,Bornholdt ZA,Aman MJ,Honko AN,Griffiths A,Dye JM,Chandran K,Lai JR
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Journal
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PLoS pathogens
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Journal Info
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2024 Apr 11;20(4):e1012134
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Abstract
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Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics. Filoviruses, including Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV), cause severe hemorrhagic fever. Although there are two FDA-approved mAb therapies for EBOV infection, these do not extend to other filoviruses. Here, we combine Fvs from broad ebolavirus mAbs to generate novel pan-ebolavirus bsAbs that are potently neutralizing, confer protection in mice, and are resistant to viral escape. Moreover, we combine Fvs from pan-ebolavirus mAbs with those of protective MARV mAbs to generate pan-filovirus protective bsAbs. These results provide guidelines for broad antiviral bsAb design and generate new immunotherapeutic candidates.
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Sequence Data
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-
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