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TB vaccine could help asthma

February 27, 2002

THE protection the BCG vaccine provides against tuberculosis is notoriously poor. But it could hold the key to a vaccine against asthma, which now affects one in seven children in the West.

       Klaus Joseph Erb`s team at the University of Würzburg in Germany gave mice nasal sprays containing the bacterium used in the BCG vaccine. When they later exposed the mice to the egg-white protein ovalbumin, which usually gives them asthma-like symptoms, their lungs remained healthy.

       The tests provide further support for the hygiene hypothesis, which blames over-cleanliness for the inexorable rise in asthma and other autoimmune diseases in the West. According to this theory, exposure to common soil bacteria shifts the immune system`s reaction to allergens from the Th2 response that causes the symptoms of allergies to the less harmful Th1 response. (New Scientist, 18 July 1998, p 26).

       These soil bacteria are closely related to the TB bug, and observations in Africa have suggested that TB and its relatives can also have a protective effect. So Erb`s team reasoned that BCG, a mild strain of the bacterium that causes TB in cows, might also protect against asthma when sprayed into the lungs.

       "The biggest surprise was that the mycobacteria didn`t have to be alive to cause the effect," says Erb. Only injections of live BCG can protect people against TB.

       Crucially, his team also showed that the balance had shifted away from the Th2 response. So-called T helper 2 (Th2) white blood cells had vanished from the mice`s lungs. Also banished were eosinophils, cells that aggravate asthma by releasing histamine.

       In their place, Erb found high levels of interferon-gamma, a messenger substance that he thinks excludes the Th2 cells. "It could be the signal saying: `Don`t come in`, or `Don`t stay`," he says.
       But both the live and killed versions of BCG caused lung inflammation in the mice, which would be unacceptable in people. "The last thing you should put into the lung of an asthmatic is something that causes even more inflammation," Erb says. "The trick is to find which components of the vaccines do the trick so you still get the benefits without any side effects."

       So he and his colleagues are testing fragments of the dead bacteria to see if any of them protect against asthma without causing inflammation. Most promising, he believes, are "CpG motifs"-slugs of bacterial DNA unusually rich in the nucleotide bases guanine and cytosine that provoke a strong immune response.

       Other groups are also developing asthma vaccines. SR Pharma of London is already carrying out trials with a heat-killed soil bacterium, Mycobacterium vaccae, which is injected into the skin. Initial results suggest it does reduce the severity of asthma and eczema in patients. But a vaccine that can be safely delivered to the lungs might be even more effective.

       Graham Rook of University College London, a cofounder of SR Pharma, adds that the focus of research is shifting away from simply trying to alter the Th2/Th1 balance. His and other groups are studying regulatory T cells that can completely block both responses.

Author: Andy Coghlan
More at: Vaccine (vol 20, p 1532)


http://www.newscientist.com New Scientist issue 2nd March 2002


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