دورية أكاديمية
Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
| العنوان: | Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model |
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| المؤلفون: | Proud, PC, Tsitoura, D, Watson, RJ, Chua, BY, Aram, MJ, Bewley, KR, Cavell, BE, Cobb, R, Dowall, S, Fotheringham, SA, Ho, CMK, Lucas, V, Ngabo, D, Rayner, E, Ryan, KA, Slack, GS, Thomas, S, Wand, N, Yeates, P, Demaison, C, Zeng, W, Holmes, I, Jackson, DC, Bartlett, NW, Mercuri, F, Carroll, MW |
| بيانات النشر: | ELSEVIER |
| سنة النشر: | 2021 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | BACKGROUND: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. METHODS: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). FINDINGS: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. INTERPRETATION: The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT, to reduce SARS-CoV-2 transmission and provide protection against COVID-19. FUNDING: This work was funded by Ena Respiratory, Melbourne, Australia. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2352-3964 |
| العلاقة: | pii: S2352-3964(20)30529-6; Proud, P. C., Tsitoura, D., Watson, R. J., Chua, B. Y., Aram, M. J., Bewley, K. R., Cavell, B. E., Cobb, R., Dowall, S., Fotheringham, S. A., Ho, C. M. K., Lucas, V., Ngabo, D., Rayner, E., Ryan, K. A., Slack, G. S., Thomas, S., Wand, N., Yeates, P. ,. Carroll, M. W. (2021). Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model. EBIOMEDICINE, 63, https://doi.org/10.1016/j.ebiom.2020.103153Test.; http://hdl.handle.net/11343/272186Test |
| الإتاحة: | https://doi.org/10.1016/j.ebiom.2020.103153Test http://hdl.handle.net/11343/272186Test |
| حقوق: | CC BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0Test |
| رقم الانضمام: | edsbas.563156D8 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 23523964 |
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