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Basic Characteristics of Mutations
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Mutation Site
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D1146Y |
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Mutation Site Sentence
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One animal in the 0.1 mg/kg treatment group exhibited mutation D1146Y present at 10% frequency at 2 dpi but was not detected within the samples taken at necropsy (Fig 5C). |
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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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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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Location
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- |
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Literature Information
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PMID
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39847599
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Title
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Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques
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Author
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Edwards CT,Karunakaran KA,Garcia E,Beutler N,Gagne M,Golden N,Aoued H,Pellegrini KL,Burnett MR,Honeycutt CC,Lapp SA,Ton T,Lin MC,Metz A,Bombin A,Goff K,Scheuermann SE,Wilkes A,Wood JS,Ehnert S,Weissman S,Curran EH,Roy M,Dessasau E,Paiardini M,Upadhyay AA,Moore IN,Maness NJ,Douek DC,Piantadosi A,Andrabi R,Rogers TR,Burton DR,Bosinger SE
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Journal
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PLoS pathogens
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Journal Info
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2025 Jan 23;21(1):e1012456
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Abstract
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The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (beta-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other beta-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-beta-CoV vaccines.
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Sequence Data
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GSE283190
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