title: Immunization by a bacterial aerosol.
abstract: 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-Guérin (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.
authors.affiliation: University of North Carolina, Chapel Hill, NC 27599-7360, USA.
authors.forename: Lucila
authors.initials: L
authors.lastname: Garcia-Contreras
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Wong
authors.forename: Pavan
authors.initials: P
authors.lastname: Muttil
authors.forename: Danielle
authors.initials: D
authors.lastname: Padilla
authors.forename: Jerry
authors.initials: J
authors.lastname: Sadoff
authors.forename: Jessica
authors.initials: J
authors.lastname: Derousse
authors.forename: Willem Andreas
authors.initials: WA
authors.lastname: Germishuizen
authors.forename: Sunali
authors.initials: S
authors.lastname: Goonesekera
authors.forename: Katharina
authors.initials: K
authors.lastname: Elbert
authors.forename: Barry R
authors.initials: BR
authors.lastname: Bloom
authors.forename: Rich
authors.initials: R
authors.lastname: Miller
authors.forename: P Bernard
authors.initials: PB
authors.lastname: Fourie
authors.forename: Anthony
authors.initials: A
authors.lastname: Hickey
authors.forename: David
authors.initials: D
authors.lastname: Edwards
mesh_terms: D000336:Aerosols / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D004333:Drug Administration Routes; D006168:Guinea Pigs; D006813:Humidity; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000382:microbiology; D007114:Immunization / Q000379:methods*; D007930:Leucine / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D050296:Microbial Viability / Q000187:drug effects; D020102:Mycobacterium smegmatis / Q000276:immunology / Q000648:ultrastructure; D013154:Spleen / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D014373:Tuberculin
chemical_list: D000336:Aerosols; D001500:BCG Vaccine; D001428:Bacterial Vaccines; D014373:Tuberculin; D007930:Leucine