Background: Vercelli and coworkers recently observed that a well-established bacterial lysate (OM-85, Vifor Pharma; CH) was able to downregulate the expression of Angiotensin-Converting Enzyme 2 (ACE2) on epithelial cells. This downregulation was also associated with a reduced infectivity of cells, resulting in a reduced viral titer. We evaluated whether another bacterial lysate (Lantigen B, Bruschettini Ltd; Italy) may have similar activities. However, while OM-85 is given per os and has a systemic effect after absorption at the gut level, Lantigen B is given locoregionally. Thus, the concentration that the bacterial lysate can reach at the mucosal level seems to be promising. Methods: Oropharyngeal cells were collected from healthy donors. After 24 h of treatment in vitro with doses of Lantigen B comparable to those that are reached in vivo, the expression of ACE2 was evaluated by direct fluorescence and flow cytometry. Results: A reduction in the number of ACE2-pos. cells was observed in 80% of treated samples. Only a few donors had poor expression of ACE2, and in these donors, the downregulation was less evident or absent. Conclusions: These results suggest that Lantigen B, at pharmacol. doses, could be an interesting drug to reduce ACE2 expression on oropharyngeal cells, thus contributing to the prophylaxis of COVID-19 in humans.