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-Gué rin (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.bacillus Calmette-Gué rin ͉ inhaled particles ͉ live-attenuated vaccines ͉ spray drying ͉ tuberculosis A erosol vaccination via the lungs targets an epithelium critical to host defense against inhaled pathogens (1), potentially avoids needle injection, and provides an exciting opportunity in the development of a newer and more effective tuberculosis (TB) vaccine. Published studies of inhaled vaccines for measles, influenza, and TB (2) have mostly involved nebulized solutions, a process that necessitates large volumes of water with long administration times; dried forms of vaccines, as formed traditionally by freeze drying and recently by spray drying (15), present an alternative to nebulization but pose risks to the integrity of dried bacteria and produce powders with suboptimal dispersive characteristics. Here, we show that by designing bacterial vaccines via rapid drying we can exploit the natural tendency of dried bacteria to assume elongated shapes and achieve remarkably effective airborne properties that combine the positive attributes of their submicrometer radial axes and micrometer-scale longitudinal axes. We demonstrate vaccine delivery from an inhaler designed for delivery to newborns. Furthermore, we report better TB protection with an aerosol form of bacillus Calmette-Guérin (BCG) than is achievable by standard s.c. and intradermal injection using a low-inoculum, aerosol infection and challenge in the sensitive guinea pig model. ResultsIn initial experiments, powders of dry bacteria were prepared by spray drying with a model nonpathogenic Mycobacterium, Mycobacterium smegmatis. We added a sec...

A plankton community unconditioned by Diacyclops thomasi predation was incubated with and without D. thomasj for 10 d to test the hypothesis that a recent manipulation of the food web of Castle Lake. CA; USA, altered phytoplankton biomass and productivity via effects of cyclopoid predation on microconsumers. Microconsumer grazing rates on bacteria and phytoplankton, ciliate abundance, chlorophyll, phytoplankton biovolume, and bacterial abundance were quantified before and after incubation. D. thomasi significantly reduced ciliate abundances relative to controls lacking D. thomasi. D. thomasj treatments also had higher chlorophyll concentration, bacterial abundance and maximum growth capacity of phytoplankton relative to controls. These results are consistent with the hypothesis that increases in D. thomasi in Castle Lake following food web manipulation affected lirnnological processes by affecting microconsumer abundances with subsequent effects on algae and bacteria.

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