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Basic Characteristics of Mutations
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Mutation Site
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N207Q |
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Mutation Site Sentence
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Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. |
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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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NS1 |
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Standardized Encoding Gene
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NS1
|
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Genotype/Subtype
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DENV-2 |
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Viral Reference
|
KM204118
|
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Functional Impact and Mechanisms
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Disease
|
Cell line
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Immune
|
- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
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Clinical Information
|
- |
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Treatment
|
- |
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Location
|
- |
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Literature Information
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PMID
|
37112626
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Title
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Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice
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Author
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Wilken L,Stelz S,Agac A,Sutter G,Prajeeth CK,Rimmelzwaan GF
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Journal
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Vaccines
|
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Journal Info
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2023 Mar 23;11(4):714
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Abstract
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The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naive individuals, sensitising them to antibody-enhanced dengue disease. DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. Prime-boost immunisation of C57BL/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4(+) T-cell responses. Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection.
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Sequence Data
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-
|
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