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Basic Characteristics of Mutations
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Mutation Site
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H270P |
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Mutation Site Sentence
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A rabies mRNA vaccine with H270P mutation in its glycoprotein induces strong cellular and humoral immunity |
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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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G |
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Standardized Encoding Gene
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RABVgp4
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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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- |
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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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38262810
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Title
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A rabies mRNA vaccine with H270P mutation in its glycoprotein induces strong cellular and humoral immunity
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Author
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Cao H,Li H,Luan N,Zhang H,Lin K,Hu J,Song J,Liu C
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Journal
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Vaccine
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Journal Info
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2024 Feb 15;42(5):1116-1121
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Abstract
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Rabies is a lethal zoonotic disease that kills approximately 60,000 people each year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates its host-cell entry. RABV-G's pre-fusion conformation displays major known neutralizing antibody epitopes, which can be used as immunogen for prophylaxis. H270P targeted mutation can stabilize RABV-G in the pre-fusion conformation. Herein, we report the development of a highly promising rabies mRNA vaccine composed of H270P targeted mutation packaged in lipid nanoparticle (LNP), named LNP-mRNA-G-H270P. Humoral and cellular immunity of this vaccine were assessed in mice comparing to the unmodified LNP-mRNA-G and a commercially available inactivated vaccine using one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test. The results show the titer of RABV-G-specific IgG and virus-neutralization antibody titers (VNTs) in LNP-mRNA-G-H270P group were significant higher than those in LNP-mRNA-G and inactivated vaccine groups. Likewise, IFN-gamma-secreting splenocytes, level of IL-2 in the supernatant of spleen cells, as well as IFN-gamma-producing CD4(+) T cells in LNP-mRNA-G-H270P group were significant higher than those in the other two vaccine groups. Hence, these results demonstrated that targeting the H270P mutation in RABV-G through an mRNA-LNP vaccine platform represents a promising strategy for developing a more efficacious rabies vaccine.
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Sequence Data
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-
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