CAMBRIDGE, Mass. - February 12, 2007 - Bioengineers and public health researchers have developed a novel spray drying method for preserving and delivering the most common tuberculosis (TB) vaccine. The low-cost and scaleable technique offers several potential advantages over conventional freezing procedures, such as greater stability at room temperature and use in needle-free delivery. The spray drying process could one day provide a better approach for vaccination against TB and help prevent the related spread of HIV/AIDS in the developing world.
The research team led by Yun-Ling Wong, a graduate researcher in bioengineering, and David Edwards, Gordon McKay Professor of the Practice of Biomedical Engineering, both at the Harvard School of Engineering and Applied Sciences, and Barry R. Bloom, Dean of the Harvard School of Public Health and Joan L. and Julius H. Jacobson Professor of Public Health, was sponsored in part by the Bill and Melinda Gates Foundation. The work appeared in the February 13 edition of the Proceedings of the National Academy of Sciences.
"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," said Wong. "An optimal new vaccine would obviate needle injection, not require refrigerated storage, and provide a safe and more consistent degree of protection."
BCG, while the most widely administered childhood vaccine in the world, with 100 million infant administrations annually, is presently dried by freezing--or lyophilization --and delivered by needle injection. The commercial formulation requires refrigerated storage and has shown variable degrees of protection against tuberculosis in different parts of the world. Because of such limitations, public health experts and physicians have long seen a need for alternatives to the traditional BCG vaccine and current treatment strategies.
"The breakthrough for developing the spray drying process involved removing salts and cryoprotectants like glycerol from bacterial suspensions," explains Edwards. "This is counter to conventional thinking: that bacteria be dried in the presence of salts and cryoprotectants. While these substances are generally required for normal storage and freezing protocols, in the case of evaporative drying as occurs in spray drying, salt and cryoprotectants act like knives that press on the bacterial membrane with great force and inactivate the bacteria. By removing these, we managed to save the bacteria and achieve better stability."
The spray drying process developed for the BCG vaccine is similar to the way manufacturers prepare powdered milk. In fact, Edwards' first exposure to the spray drying process occurred when he was working with a spray dryer to produce highly respirable drug aerosols in a food science lab. While spray drying of small and large molecules is common in the food, cosmetic and pharmaceutical industries, the method has not been commonly used for drying cellular material. Most important, the new technique enables the BCG vaccine, and potentially other bacterial and viral based vaccines, to be dried without the traditional problems associated with standard freezing.
"Unlike traditional freezing techniques, spray drying is lower cost, easily scaleable for manufacturing, and ideal for use in aerosol (needle free) formulations, such as inhalation," says Wong. "Its greater stability at room temperature and viability ultimately could provide a more practical approach for creating and delivering a vaccine throughout the world."
Edwards, an international leader in aerosol drug and vaccine delivery, sees great promise for the advance, which he and his colleagues hope to develop in the next few years for better vaccination approaches for diseases of poverty through the international not-for-profit Medicine in Need (Mend), based in Cambridge, Paris, and Cape Town, South Africa.
"With the emergence of multidrug and extremely drug resistant TB, we hope this breakthrough is one more step to help us develop a stable vaccine to stem the tide of disease," says Bloom. "Better vaccination against TB can go a long way to addressing the current developing world health care crisis, with TB alone presently taking the lives of more than 2 million people a year. And we believe this method could also be used to improve delivery of many other vaccines."
Wong, Edwards, and Bloom's co-authors included Samantha Sampson and Sunali Goonesekera (Harvard School of Public Health); Willem Andreas Germishuizen (Harvard School of Engineering and Applied Sciences); Giovanni Caponetti (Eratech), Jerry Sadoff (Aeras Global TB Vaccine Foundation). The work was supported by a Grand Challenge Grant from the Bill and Melinda Gates Foundation and with a grant from the National Institutes of Health.