A new powdered form of tuberculosis (TB) vaccine may help save some of the nearly two million lives lost to the disease annually. In preliminary tests, the powdered form contained more active bacterial cells than a freeze-dried version similar to the existing vaccine. The result may pave the way for health workers to administer the vaccine as an aerosol to the lungs instead of as an injection, possibly leading to a more effective treatment.

If combined with other changes to the current tuberculosis vaccine, called BCG, the drying technique could help save hundreds of thousands of lives, says Jerry Sadoff, president and CEO of the Aeras Global TB Vaccine Foundation and co-author of a report describing the advance.

"This is a very important technological advance," says immunologist Stefan Kaufmann of the Max Planck Institute for Infection Biology in Berlin, who was not involved in the study. "It will allow needle-free administration of BCG, which is particularly important for developing countries."

The BCG vaccine, which health workers administer to 100 million infants annually, consists of a weakened mycobacterium from cows that is related to the human TB mycobacterium. Researchers believe that the vaccine saves 40,000 to 100,000 lives annually by preventing the spread of TB from the lungs to the brain and other organs. But BCG is freeze-dried much like instant coffee, which damages the mycobacteria and creates particles that are too big to be inhaled. Researchers suspect than an inhalant vaccine would be more effective, because "tuberculosis is primarily a disease of the lung," Kaufmann says.

In an attempt to create such a product, Sadoff and his colleagues turned to a method called spray-drying, used to make powdered milk. In spray-drying, a mixture of water and the material to be dried is forced through a sprinkler into a high-temperature drum, instantly evaporating the water droplets clinging to the material.

Bacteria tend to die during spray-drying as well, but the researchers suspected that the problem might lie with additives such as salt and glycerol, which are essential to freeze-drying and were used in prior spray-drying procedures. So they left out those chemicals and instead added the amino acid leucine to soak up any remaining moisture.

The researchers found that 50 percent of the BCG mycobacteria survived the spray-drying process, compared with 5 percent when the same solution was freeze-dried, according to a paper published online recently by the Proceedings of the National Academy of Sciences USA.

"By having less damage in the dried form we should have a better vaccine," says bioengineer David Edwards of Harvard University, a co-author of the report. He adds that spray-drying would be simpler and cheaper to implement on large scales than freeze-drying.

The BCG vaccine has over the decades lost its effectiveness against TB lung infections, the most common form of the illness. "Why it doesn't work anymore is a mystery—a big mystery," Sadoff says. Part of the problem, he says, may be BCG's old-fashioned manufacturing process, including the freeze-drying step, so incorporating spray-drying may help introduce a more effective vaccine.

Sadoff says clinical tests of spray-dried BCG could begin as soon as late 2008, when his group plans to conduct mid-stage trials of several new forms of the vaccine. Edwards adds that the South African NGO Medicine in Need has begun implementing the manufacturing tools for spray-drying.

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