tetano
Editor, Senior Moderator
J Allergy Clin Immunol
. 2021 Dec 10;S0091-6749(21)02581-1.
doi: 10.1016/j.jaci.2021.11.019. Online ahead of print.
The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression
Vadim Pivniouk, Oksana Pivniouk, Avery DeVries, Jennifer L Uhrlaub, Ashley Michael, Denis Pivniouk, Sydney R VanLinden, Michelle Y Conway, Seongmin Hahn, Sean P Malone, Peace Ezeh, Jared M Churko, Dayna Anderson, Monica Kraft, Janko Nikolich-Zugich, Donata Vercelli
Abstract
Background: Treatments for coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with ACE2 and TMPRSS2 on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions.
Objectives: To investigate whether and how OM-85 treatment protects non-human primate and human epithelial cells against SARS-CoV-2.
Methods: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro.
Results: OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation.
Conclusion: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of COVID-19.
Keywords: ACE2; Bacterial lysate; COVID-19; Epithelial cells; OM-85; SARS-CoV-2,; TMPRSS2.
. 2021 Dec 10;S0091-6749(21)02581-1.
doi: 10.1016/j.jaci.2021.11.019. Online ahead of print.
The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression
Vadim Pivniouk, Oksana Pivniouk, Avery DeVries, Jennifer L Uhrlaub, Ashley Michael, Denis Pivniouk, Sydney R VanLinden, Michelle Y Conway, Seongmin Hahn, Sean P Malone, Peace Ezeh, Jared M Churko, Dayna Anderson, Monica Kraft, Janko Nikolich-Zugich, Donata Vercelli
- PMID: 34902435
- DOI: 10.1016/j.jaci.2021.11.019
Abstract
Background: Treatments for coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with ACE2 and TMPRSS2 on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions.
Objectives: To investigate whether and how OM-85 treatment protects non-human primate and human epithelial cells against SARS-CoV-2.
Methods: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro.
Results: OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation.
Conclusion: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of COVID-19.
Keywords: ACE2; Bacterial lysate; COVID-19; Epithelial cells; OM-85; SARS-CoV-2,; TMPRSS2.
