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PHYSICAL SCIENCES / BIOLOGICAL SCIENCES / ENGINEERING / APPLIED BIOLOGICAL SCIENCES
Drying a tuberculosis vaccine without freezing

Yun-Ling Wong^*, Samantha Sampson, Willem Andreas Germishuizen^*, Sunali Goonesekera, Giovanni Caponetti, Jerry Sadoff, Barry R. Bloom^,¶, and David Edwards^*,||

*Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115; Eratech S.r.l., 29100 Piacenza, Italy; and Aeras Global TB Vaccine Foundation, 1405 Research Boulevard, Suite 300, Rockville, MD 20850

Contributed by Barry R. Bloom, December 21, 2006 (received for review October 5, 2006)

With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette–Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, "vial-fillable" powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4°C and 25°C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.

aerosolization | bacillus Calmette–Guérin | spray drying | dry powder | mycobacterium

The authors declare no conflict of interest.

^¶To whom correspondence may be addressed at Harvard School of Public Health, 1005 Kresge, 677 Huntington Avenue, Boston, MA 02115. E-mail: bbloom{at}hsph.harvard.edu

^||To whom correspondence may be addressed at: Harvard University, 322 Pierce Hall, 29 Oxford Street, Cambridge, MA 02138. E-mail: dedwards{at}deas.harvard.edu

© 2007 by The National Academy of Sciences of the USA

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This article has been cited by other articles in HighWire Press-hosted journals:

				L. Garcia-Contreras, Y.-L. Wong, P. Muttil, D. Padilla, J. Sadoff, J. DeRousse, W. A. Germishuizen, S. Goonesekera, K. Elbert, B. R. Bloom, et al. Immunization by a bacterial aerosol PNAS, March 25, 2008; 105(12): 4656 - 4660. [Abstract] [Full Text] [PDF]

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