Author: Vineet D. Menachery; Lisa E. Gralinski; Hugh D. Mitchell; Kenneth H. Dinnon; Sarah R. Leist; Boyd L. Yount; Eileen T. McAnarney; Rachel L. Graham; Katrina M. Waters; Ralph S. Baric
Title: Combination attenuation offers strategy for live-attenuated coronavirus vaccines Document date: 2018_4_28
ID: 3t75dbb7_17
Snippet: In this manuscript, we expand upon a live-attenuated vaccine approach based on 69 mutation of coronavirus NSP16, a 2'O methyl-transferase. Previous work in murine hepatitis 70 virus, SARS-CoV, and MERS-CoV have found that disruption of NSP16 activity rendered an 71 attenuated strain sensitive to the activity of interferon stimulated IFIT1 (18) (19) (20) . Work by our 72 group went on to show that NSP16 mutants provided protection from lethal chal.....
Document: In this manuscript, we expand upon a live-attenuated vaccine approach based on 69 mutation of coronavirus NSP16, a 2'O methyl-transferase. Previous work in murine hepatitis 70 virus, SARS-CoV, and MERS-CoV have found that disruption of NSP16 activity rendered an 71 attenuated strain sensitive to the activity of interferon stimulated IFIT1 (18) (19) (20) . Work by our 72 group went on to show that NSP16 mutants provided protection from lethal challenge by both 73 SARS-CoV and MERS-CoV in young animals (19, 20) . In this work, we set forth to evaluate 74 NSP16 attenuation as a platform strategy for live-attenuated coronavirus vaccines. Using 75 models that explore heterologous challenge, efficacy in aging, and potential for reversion, we 76 found that the NSP16 mutant alone was not sufficiently attenuated to be used universally.
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