By manufacturing a single-particle system in two particulate forms (i.e., micrometer size and nanometer size), we have designed a bacterial vaccine form that exhibits improved efficacy of immunization. Microstructural properties are adapted to alter dispersive and aerosol properties independently. Dried nanomicroparticle vaccines possess two axes of nanoscale dimensions and a third axis of micrometer dimension; the last one permits effective micrometer-like physical dispersion, and the former provides alignment of the principal nanodimension particle axes with the direction of airflow. Particles formed with this combination of nano- and micrometer-scale dimensions possess a greater ability to aerosolize than particles of standard spherical isotropic shape and of similar geometric diameter. Here, we demonstrate effective application of this biomaterial by using the live attenuated tuberculosis vaccine Bacille Calmette-Guerin (BCG). Prepared as a spray-dried nanomicroparticle aerosol, BCG vaccine exhibited high-efficiency delivery and peripheral lung targeting capacity from a low-cost and technically simple delivery system. Aerosol delivery of the BCG nanomicroparticle to normal guinea pigs subsequently challenged with virulent Mycobacterium tuberculosis significantly reduced bacterial burden and lung pathology both relative to untreated animals and to control animals immunized with the standard parenteral BCG.
Garcia-Contreras, L.; Wong, Y-L.; Muttil, P.; Padilla, D.; Sadoff, J.; De Rousse, J.; Germishuizen, W.A.; Goonesekera, S.; Elbert, K.; Bloom, B.R.; Miller, R.; Fourie, P.B.; Hickey, A.; Edwards, D. Immunization by a bacterial aerosol. Proceedings of the National Academy of Sciences (2008) 105 (12) 4656-4660. [DOI: 10.1073/pnas.0800043105]