tetano
Editor, Senior Moderator
EBioMedicine
. 2020 Dec 3;63:103153.
doi: 10.1016/j.ebiom.2020.103153. Online ahead of print.
Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
Pamela C Proud[SUP] 1 [/SUP], Daphne Tsitoura[SUP] 2 [/SUP], Robert J Watson[SUP] 1 [/SUP], Brendon Y Chua[SUP] 3 [/SUP], Marilyn J Aram[SUP] 1 [/SUP], Kevin R Bewley[SUP] 1 [/SUP], Breeze E Cavell[SUP] 1 [/SUP], Rebecca Cobb[SUP] 1 [/SUP], Stuart Dowall[SUP] 1 [/SUP], Susan A Fotheringham[SUP] 1 [/SUP], Catherine M K Ho[SUP] 1 [/SUP], Vanessa Lucas[SUP] 1 [/SUP], Didier Ngabo[SUP] 1 [/SUP], Emma Rayner[SUP] 1 [/SUP], Kathryn A Ryan[SUP] 1 [/SUP], Gillian S Slack[SUP] 1 [/SUP], Stephen Thomas[SUP] 1 [/SUP], Nadina I Wand[SUP] 1 [/SUP], Paul Yeates[SUP] 1 [/SUP], Christophe Demaison[SUP] 2 [/SUP], Weiguang Zeng[SUP] 3 [/SUP], Ian Holmes[SUP] 2 [/SUP], David C Jackson[SUP] 3 [/SUP], Nathan W Bartlett[SUP] 4 [/SUP], Francesca Mercuri[SUP] 5 [/SUP], Miles W Carroll[SUP] 6 [/SUP]
Affiliations
Abstract
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 ? 10[SUP]6[/SUP] 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.
Keywords: COVID-19; Ferret; INNA-051; SARS-CoV-2; TLR-2; Viral shedding.
. 2020 Dec 3;63:103153.
doi: 10.1016/j.ebiom.2020.103153. Online ahead of print.
Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
Pamela C Proud[SUP] 1 [/SUP], Daphne Tsitoura[SUP] 2 [/SUP], Robert J Watson[SUP] 1 [/SUP], Brendon Y Chua[SUP] 3 [/SUP], Marilyn J Aram[SUP] 1 [/SUP], Kevin R Bewley[SUP] 1 [/SUP], Breeze E Cavell[SUP] 1 [/SUP], Rebecca Cobb[SUP] 1 [/SUP], Stuart Dowall[SUP] 1 [/SUP], Susan A Fotheringham[SUP] 1 [/SUP], Catherine M K Ho[SUP] 1 [/SUP], Vanessa Lucas[SUP] 1 [/SUP], Didier Ngabo[SUP] 1 [/SUP], Emma Rayner[SUP] 1 [/SUP], Kathryn A Ryan[SUP] 1 [/SUP], Gillian S Slack[SUP] 1 [/SUP], Stephen Thomas[SUP] 1 [/SUP], Nadina I Wand[SUP] 1 [/SUP], Paul Yeates[SUP] 1 [/SUP], Christophe Demaison[SUP] 2 [/SUP], Weiguang Zeng[SUP] 3 [/SUP], Ian Holmes[SUP] 2 [/SUP], David C Jackson[SUP] 3 [/SUP], Nathan W Bartlett[SUP] 4 [/SUP], Francesca Mercuri[SUP] 5 [/SUP], Miles W Carroll[SUP] 6 [/SUP]
Affiliations
- PMID: 33279857
- DOI: 10.1016/j.ebiom.2020.103153
Abstract
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 ? 10[SUP]6[/SUP] 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.
Keywords: COVID-19; Ferret; INNA-051; SARS-CoV-2; TLR-2; Viral shedding.