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Basic Characteristics of Mutations
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Mutation Site
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K986P |
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Mutation Site Sentence
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This engineered S protein includes two proline substitutions (K986P, V987P) and a mutation at the cleavage site (RRAR to QQAQ), aimed at enhancing both its stability and immunogenicity. |
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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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-
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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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China |
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Literature Information
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PMID
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39772238
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Title
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Development and Evaluation of a Newcastle Disease Virus-like Particle Vaccine Expressing SARS-CoV-2 Spike Protein with Protease-Resistant and Stability-Enhanced Modifications
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Author
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Chen Y,Tian F,Hu S,Liu X
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Journal
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Viruses
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Journal Info
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2024 Dec 18;16(12):1932
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Abstract
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The ongoing global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the continuous development of innovative vaccine strategies, especially in light of emerging viral variants that could undermine the effectiveness of existing vaccines. In this study, we developed a recombinant virus-like particle (VLP) vaccine based on the Newcastle Disease Virus (NDV) platform, displaying a stabilized prefusion form of the SARS-CoV-2 spike (S) protein. This engineered S protein includes two proline substitutions (K986P, V987P) and a mutation at the cleavage site (RRAR to QQAQ), aimed at enhancing both its stability and immunogenicity. Using a prime-boost regimen, we administered NDV-VLP-S-3Q2P intramuscularly at different doses (2, 10, and 20 microg) to BALB/c mice. Robust humoral responses were observed, with high titers of S-protein-specific IgG and neutralizing antibodies against SARS-CoV-2 pseudovirus, reaching titers of 1:2200-1:2560 post-boost. The vaccine also induced balanced Th1/Th2 immune responses, evidenced by significant upregulation of cytokines (IFN-gamma, IL-2, and IL-4) and S-protein-specific IgG1 and IgG2a. Furthermore, strong activation of CD4+ and CD8+ T cells in the spleen and lungs confirmed the vaccine's ability to promote cellular immunity. These findings demonstrate that NDV-S3Q2P-VLP is a potent immunogen capable of eliciting robust humoral and cellular immune responses, highlighting its potential as a promising candidate for further clinical development in combating COVID-19.
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Sequence Data
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-
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