Intranasal administration of DSM 32444 spores: safety and tolerability.

Administered nasally, spores of the Gram-positive bacterium have been shown to be able to induce innate immunity sufficient to confer protection to influenza and respiratory syncytial virus. Although members of the aerobiome, intranasal delivery of high numbers of live spores carries potential safety issues. To address the potential safety risk of using live spores, we assessed the safety of spores that had been completely inactivated using heat sterilization. Using autoclaved, and therefore killed, spores of a generally recognized as safe-notified strain (DSM 32444), safety was assessed (biotype, genome and cell based cytoxicity) and , using intranasal administration in rodent models and lastly in human volunteers. Using a 15-day, repeat-dose, regimen in a rodent model, no indication of toxicity was observed. In a registered human study (NCT05984004), a formulated preparation of inactivated DSM 32444 spores referred to as SPEROVID was developed, and tolerance in human volunteers was assessed following 7 days of nasal dosing (2-4 times/day). Our study demonstrated that in humans an intranasal dose of up to 3×10 killed spores was safe and well tolerated.