title: Drying a tuberculosis vaccine without freezing.
abstract: 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 degrees C and 25 degrees 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.
authors.affiliation: Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Wong
authors.forename: Samantha
authors.initials: S
authors.lastname: Sampson
authors.forename: Willem Andreas
authors.initials: WA
authors.lastname: Germishuizen
authors.forename: Sunali
authors.initials: S
authors.lastname: Goonesekera
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caponetti
authors.forename: Jerry
authors.initials: J
authors.lastname: Sadoff
authors.forename: Barry R
authors.initials: BR
authors.lastname: Bloom
authors.forename: David
authors.initials: D
authors.lastname: Edwards
mesh_terms: D000336:Aerosols; D015169:Colony Count, Microbial; D003890:Desiccation; D004356:Drug Storage / Q000379:methods*; D005615:Freezing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000302:isolation & purification / Q000648:ultrastructure; D032581:Tuberculosis Vaccines
chemical_list: D000336:Aerosols; D032581:Tuberculosis Vaccines; D049452:Green Fluorescent Proteins; D007930:Leucine