The SARS-CoV-2 Cellular Receptor ACE2 is expressed in Oropharyngeal Cells and is modulated in vitro by the Bacterial Lysate Lantigen B

Author(s): Caterina Pizzimenti, Antonella D’Agostino, Paola Pirrello, Alessia Ruiba, Giovanni Melioli

Angiotensin-converting enzyme2 (ACE2) is the main cell surface receptor of the SARS-CoV-2 spike protein and is expressed in a variety of cell types, including cells of the respiratory tract. A bacterial lysate used for the prophylaxis of respiratory infections (OM-85), was recently shown to downregulate the expression of ACE2 in epithelial cells, suggesting its possible role as a prophylaxis of the onset of COVID19. Another bacterial lysate (Lantigen B, administered sublingually) is used in the prophylaxis of recurrent respiratory tract infections. It contains antigens obtained by chemical lysis from the most representative microbes of the respiratory tract. In this in vitro study, the capacity of Lantigen B to decrease ACE2 in human oropharyngeal cells was evaluated. The study was carried out in 40 healthy donors undergoing oropharyngeal swab for routine SARS-CoV-2 detection. Cells were treated in vitro with a 1:2 of Lantigen B. ACE2 expression was evaluated using a fluorescent anti-ACE2 monoclonal antibody and flow cytometry. A reduction in the number of positive cells was observed in 72% of the patients, while a modulation of ACE2 expression was observed in 62% of the samples. As a control, the expression of the CD54 rhinovirus receptor in the same cells was unaffected. To evaluate the functional effects of down regulation, in a subset of samples, the same oropharynx cells were incubated with Lantigen B and infected with wild-type SARS-CoV-2. After 24 hours, viral RNA, as assessed by rt-PCR, was significantly lower in samples treated with Lantigen B. In conclusion, this study demonstrates that Lantigen B, at a pharmacological dose, modulates the expression of the main SARS-CoV-2 receptor in oropharyngeal cells, and reduces viral yield. This activity could be synergistic with other approaches (vaccination and therapy) by reducing the number of potentially infected cells and thus reducing the effects of SARSCoV- 2 inf