Particle Dynamics and Bioaerosol Viability of Aerosolized BCG Vaccine Using Jet and Vibrating Mesh Clinical Nebulizers

Abstract

AbstractBackgroundBacillus Calmette–Guérin (BCG) is a vaccine used to protect against tuberculosis primarily in infants to stop early infection in areas of the world where the disease is endemic. Normally administered as a percutaneous injection, BCG is a live, significantly attenuated bacteria that is now being investigated for its potential within an inhalable vaccine formulation. This work investigates the feasibility and performance of four jet and ultrasonic nebulizers aerosolizing BCG and the resulting particle characteristics and residual viability of the bacteria post-aerosolization.MethodsA jet nebulizer (Collison) outfitted either with a 3- or 6-jet head, was compared to two clinical nebulizers, the vibrating mesh Omron MicroAir and Aerogen Solo devices. Particle characteristics, including aerodynamic particle sizing, was performed on all devices within a common aerosol chamber configuration and comparable BCG innocula concentrations. Integrated aerosol samples were collected for each generator and assayed for bacterial viability using conventional microbiological technique.Results and ConclusionsA batch lot of BCG (Danish) was grown to titer and used in all generator assessments. Aerosol particles within the respirable range were generated from all nebulizers at four different concentrations of BCG. The jet nebulizers produced a uniformly smaller particle size than the ultrasonic devices, although particle concentrations by mass were similar across all devices tested with the exception of the Aerogen Solo, which resulted in a very low concentration of BCG aerosols. The resulting measured viable BCG aerosol concentration fraction produced by each device approximated one another; however, a measurable decrease of efficiency and overall viability reduction in the jet nebulizer was observed in higher BCG inoculum starting concentrations, whereas the vibrating mesh nebulizer returned a remarkably stable viable aerosol fraction irrespective of inoculum concentration.