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Basic Characteristics of Mutations
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Mutation Site
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V987P |
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Mutation Site Sentence
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In contrast, we found superior S1 cell surface presentation upon infection with a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein with an inactivated S1/S2 cleavage site and K986P and V987P mutations (MVA-SARS-2-ST). |
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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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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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- |
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Viral Reference
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MN908947.3
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Functional Impact and Mechanisms
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Disease
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COVID-19
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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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Germany |
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Literature Information
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PMID
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36301637
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Title
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Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity
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Author
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Meyer Zu Natrup C,Tscherne A,Dahlke C,Ciurkiewicz M,Shin DL,Fathi A,Rohde C,Kalodimou G,Halwe S,Limpinsel L,Schwarz JH,Klug M,Esen M,Schneiderhan-Marra N,Dulovic A,Kupke A,Brosinski K,Clever S,Schunemann LM,Beythien G,Armando F,Mayer L,Weskamm ML,Jany S,Freudenstein A,Tuchel T,Baumgartner W,Kremsner P,Fendel R,Addo MM,Becker S,Sutter G,Volz A
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Journal
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The Journal of clinical investigation
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Journal Info
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2022 Dec 15;132(24):e159895
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Abstract
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The SARS-CoV-2 spike (S) glycoprotein is synthesized as a large precursor protein and must be activated by proteolytic cleavage into S1 and S2. A recombinant modified vaccinia virus Ankara (MVA) expressing native, full-length S protein (MVA-SARS-2-S) is currently under investigation as a candidate vaccine in phase I clinical studies. Initial results from immunogenicity monitoring revealed induction of S-specific antibodies binding to S2, but low-level antibody responses to the S1 domain. Follow-up investigations of native S antigen synthesis in MVA-SARS-2-S-infected cells revealed limited levels of S1 protein on the cell surface. In contrast, we found superior S1 cell surface presentation upon infection with a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein with an inactivated S1/S2 cleavage site and K986P and V987P mutations (MVA-SARS-2-ST). When comparing immunogenicity of MVA vector vaccines, mice vaccinated with MVA-SARS-2-ST mounted substantial levels of broadly reactive anti-S antibodies that effectively neutralized different SARS-CoV-2 variants. Importantly, intramuscular MVA-SARS-2-ST immunization of hamsters and mice resulted in potent immune responses upon challenge infection and protected from disease and severe lung pathology. Our results suggest that MVA-SARS-2-ST represents an improved clinical candidate vaccine and that the presence of plasma membrane-bound S1 is highly beneficial to induce protective antibody levels.
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Sequence Data
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-
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