June 6-11, 2010
Mycobacterium bovis BCG is the current vaccine for tuberculosis (TB). However, BCG as it is currently administered shows highly variable efficacy in protecting adults against TB. The natural route of infection of TB is via inhalation of bacilli-containing aerosols and it is postulated that immunization by the natural route of infection may lead to a greater immunity given the fact that the lungs are the primary target of infection. By eliciting both local and systemic immune responses, it is anticipated that an inhaled form of BCG will offer greater protection against pulmonary TB.
Current commercial BCG vaccine preparations are filled as bacterial suspensions in vials, dried through lyophilization and stabilized through refrigeration with a one year shelf life. However, freeze-dried BCG does not exhibit a particle form conducive for delivery via the aerosol route and must be injected. Spray drying studies by Harvard University and Medicine in Need (MEND) scientists have demonstrated that BCG could be spray dried into a viable aerosol with up to 1 year of stability under refrigerated conditions, with the potential for room temperature stability.
To support the further preclinical development of the BCG aerosol for application in the developing world, MEND established a state-of-the-art Biosafety level 3 spray drying facility with local expertise in South Africa, where the vaccine will be produced for an IND-enabling toxicology study meeting OECD Good Laboratory Practice (GLP) requirements. Frozen BCG bulk is spray dried and the resulting dry powder is characterized in terms of viability and aerosol properties. The dried BCG aerosol is then aseptically filled into capsules using a semi-automatic filling device for delivery using a low-cost hand-held inhaler.
In conclusion, the spray drying technology was successfully transferred from Harvard University to the MEND facility in Pretoria. MEND is developing local expertise and infrastructure to support further preclinical and clinical development of BCG for inhalation.
Willem Germishuizen, L Venter, A Khosa, F Mudau, P.B. Fourie, B Pulliam, M Kabadi, A Schiermeier, and D.A . Edwards, "ESTABLISHING A PLATFORM FOR SPRAY DRYING INHALABLE VACCINES IN SOUTH AFRICA" in "Vaccine Technology III", John G. Auniņš,Merck, USA; Barry C. Buckland, BiologicB, USA; Kathrin U. Jansen, Pfizer, USA; Paula Marques Alves, IBET, Portugal Eds, ECI Symposium Series, (2010). http://dc.engconfintl.org/vaccine_iii/21