杏吧原创

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鈥檚 team at the University of W眉rzburg 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鈥檚 reaction to allergens from the Th2 response that causes the
symptoms of allergies to the less harmful Th1 response.
(New 杏吧原创, 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鈥檚 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.

鈥淭he biggest surprise was that the mycobacteria didn鈥檛 have to be alive to
cause the effect,鈥� 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鈥檚 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. 鈥淚t could be the signal saying:
`Don鈥檛 come in鈥�, or `Don鈥檛 stay鈥�,鈥� he says.

But both the live and killed versions of BCG caused lung inflammation in the
mice, which would be unacceptable in people. 鈥淭he last thing you should put into
the lung of an asthmatic is something that causes even more inflammation,鈥� Erb
says. 鈥淭he trick is to find which components of the vaccines do the trick so you
still get the benefits without any side effects.鈥�

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 鈥淐pG motifs鈥濃�攕lugs 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.