杏吧原创

THE existing vaccine for tuberculosis is a gamble鈥攕ometimes it works,
sometimes it doesn鈥檛. But now, in a breakthrough that could save millions of
lives, immunologists have figured out why it is so hit or miss, and how to fix
the problem.

TB is caused by a bacterium that spreads through the air and infects the
lungs. Not everyone who is infected gets sick, but the disease is so prevalent
in regions like Africa that it鈥檚 responsible for a quarter of preventable adult
deaths. You can treat the infections, but more and more resist standard drugs,
so a better vaccine is sorely needed.

The standard vaccine, developed in the 1920s, is a weakened strain of
Mycobacterium bovis, the bacterium that gives cattle TB. The jab is called
Bacillus Calmette-Gu茅rin, or BCG. While the vaccine has saved millions of
lives, it still fails to prevent TB in as many as 80 per cent of the people who
get the shots.

鈥淣ow we have a good explanation for the failure of BCG, and have found a way
round the problem,鈥� says Peter Andersen, head of the team which made the
discovery at the Danish government鈥檚 State Serum Institute in Copenhagen.

Through experiments on mice, his team has pinned the blame on weaker
relatives of Mycobacterium tuberculosis, the bug that causes TB in
people. Favouring the soil, water and food of hot countries, these strains
accidentally sabotage the vaccine by getting to people first. 鈥淓ssentially, they
immunise people against BCG,鈥� says Andersen, by preventing the BCG vaccine from
multiplying inside the body. But these related bacteria don鈥檛 themselves trigger
enough immunity to protect against TB. The theory also explains why BCG will
protect infants if they鈥檙e injected just after birth, before environmental
mycobacteria can get in the way.

Andersen and his team proved the link by infecting mice with three related
strains of mycobacteria, all of them isolated from patients and soil in parts of
Malawi where BCG doesn鈥檛 work. In each case, subsequent BCG shots failed to stop
the mice getting TB.

Paul Fine, professor of communicable disease epidemiology at the London
School of Hygiene and Tropical Medicine, says that the paper 鈥渃omes up with the
best evidence yet鈥� that prior exposure to related bacteria nullifies BCG. But he
cautions that despite BCG鈥檚 failure to protect against TB in Malawi, it did
protect against another mycobacterium鈥攖he one that causes leprosy. That
doesn鈥檛 tally with the theory that the early exposure to mycobacteria completely
knocks out the effectiveness of BCG.

The good news is that new vaccines made from fragments of dead TB bacteria
did protect the pre-infected mice from TB. Unlike the live BCG vaccines, these
inanimate assemblies don鈥檛 need to multiply in the body to be effective.

鈥淭here are many such vaccines in the pipeline,鈥� says Andersen, though only
one has so far reached the stage of clinical trials
(New 杏吧原创, 27 October 2001, p 11).
The big hope, says Andersen, is that these new vaccines
might provide immunity for adolescents whose BCG protection has either worn off
or never took hold in the first place.