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Basic Characteristics of Mutations
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Mutation Site
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A241T |
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Mutation Site Sentence
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We isolated 43 viruses following exposure to CR6261, from which 16 carried an F227L mutation in the HA and eight carried A241T mutation in the HA (Figure 3B). |
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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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HA |
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Standardized Encoding Gene
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HA
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Genotype/Subtype
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H1N1 |
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Viral Reference
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956529
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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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39086132
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Title
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Dual neutralization of influenza virus hemagglutinin and neuraminidase by a bispecific antibody leads to improved antiviral activity
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Author
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Moirangthem R,Cordela S,Khateeb D,Shor B,Kosik I,Schneidman-Duhovny D,Mandelboim M,Jonsson F,Yewdell JW,Bruel T,Bar-On Y
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Journal
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Molecular therapy : the journal of the American Society of Gene Therapy
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Journal Info
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2024 Oct 2;32(10):3712-3728
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Abstract
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Targeting multiple viral proteins is pivotal for sustained suppression of highly mutable viruses. In recent years, broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed, and antibody monotherapy has been tested in preclinical and clinical studies to treat or prevent influenza virus infection. However, the impact of dual neutralization of the hemagglutinin and neuraminidase on the course of infection, as well as its therapeutic potential, has not been thoroughly tested. For this purpose, we generated a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase of influenza viruses. We demonstrated that this bispecific antibody has a dual-antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over monoclonal antibody combination as it resulted an improved neutralization capacity and augmented the antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice, reduced mice mortality, and limited the virus mutation profile upon antibody administration. Thus, dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.
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Sequence Data
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-
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