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BACTERIA that cause typhoid or miscarriages are being manipulated to produce
vaccines against deadly diseases, including AIDS. Loaded with fragments of HIV
or other pathogens, the bacteria act as a radical new kind of cheap vaccine that
can be swallowed instead of injected. If the vaccine causes any problems,
antibiotics will destroy it.

One such HIV vaccine, developed by David Hone and his colleagues at the
University of Maryland Biotechnology Institute in Baltimore, is based on a
weakened form of Salmonella typhi, the bacterium that causes typhoid
fever. Hone hopes to start testing the vaccine later this year in Nigeria and
Uganda.

The other, developed by Yvonne Paterson and her colleagues at the University
of Pennsylvania Medical School in Philadelphia, is based on Listeria
monocytogenes. This bacterium can cause pregnant women to miscarry and
triggers meningitis in people with weakened immunity. But otherwise it poses few
problems in healthy people.

鈥淭hey are revolutionary vaccines,鈥� says Paterson, who has shown the vaccine
works as planned in mice. She is now applying to test the vaccine in
macaques.

The new concoctions have been dubbed 鈥淭rojan horse鈥� vaccines because the live
bacteria invade and occupy white blood cells lining the gut. Researchers working
with Salmonella have chosen a strain which invades cells but is too
weak to cause disease. Paterson hopes to find an equally benign strain of
Listeria, but her initial experiments have used the natural strain.

The cells invaded include sentinels of the immune system called dendritic
cells. These teach the immune system which invading bugs to attack. Usually,
they engulf and 鈥渃hew up鈥� any alien bacteria or viruses that they encounter, and
then show bits of the dismembered bugs to other cells of the immune system, such
as killer T cells. These are then primed to recognise and attack the real
invader.

Salmonella and Listeria have both evolved ways to hide in
white blood cells without being destroyed. To turn them into vaccines against
AIDS, the research teams have equipped them with genes from HIV. Proteins made
by these viral genes are chewed up and displayed in the normal way when
dendritic cells meet the altered bacteria. In this way, the immune system learns
to recognise and attack regions of real HIV if infection occurs.

Tests on animals treated with the salmonella vaccine have shown that it can
protect the mucosal surfaces where HIV normally enters the body, such as the
cervix, vagina and rectum. It does this by producing antibodies and priming T
cells. 鈥淵ou get immunity at mucosal surfaces and that鈥檚 where HIV infects,鈥� says
Paterson.

Ray Spier, a vaccine specialist at the University of Surrey, says that the
approach is exciting but fears that booster doses might be needed. 鈥淢ucosal
immunity is sometimes short-lived, just weeks or months instead of years,鈥� he
says.