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Women are particularly at risk from HIV infection because
the efficiency of HIV transmission from men to women is
greater than for women to men, say the researchers. But in the
absence of a vaccine, there are very few ways for women to
protect themselves.
The main way that women get infected with HIV is through
the vaginal mucosa. In healthy women, this tissue layer is
populated with a number of bacterial species, dominated by
lactobacilli, forming a dynamic ecosystem. However, if the
lactobacilli are depleted or disturbed, harmful bacteria can
become established and there is an increased risk of infection
with HIV.
So Peter P. Lee, assistant professor at the Department of
Medicine, Stanford University, had the idea that this
protective role of the vaginal microflora might be enhanced by
genetic engineering to form a "shield" against diseases such
as HIV.
He and his colleagues began by genetically modifying
naturally occurring Lactobacillus jensenii so that it
secretes CD4, a protein that is usually found on the surface
of immune cells. HIV binds to this protein and uses it to
infiltrate the cells.
"In a sense, we're trying to express a decoy receptor for
HIV," said co-author John Lewicki, vice president of research
and development at Osel Incorporated, Santa Clara, California.
The researchers hypothesized that the protein would bind the
viruses in the mucosal layer and so impede their access to the
underlying cells.
In a proof-of-concept paper published in the Proceedings
of the National Academy of Sciences, the researchers show
that the CD4 produced by the engineered bacteria does bind to
HIV-1, and can inhibit the infection of cultured cells with a
laboratory strain of HIV-1.
"This is a wonderful approach to prevent vaginal
transmission of HIV," said David Montefiori, research
professor in the department of surgery at Duke University
Medical Center, North Carolina, who studies antibodies that
neutralize HIV. "It's a novel approach that could be much more
feasible and practical for women than the approaches that most
other people are taking."
Lewicki is keen to point out that the work is only a first
step towards a clinical product. "CD4 is relatively
ineffective at neutralizing clinical strains of HIV," he
noted. But the scientists are working on ways to make the CD4
more effective at binding the HIV.
One of their approaches is to alter the CD4 so that it
sticks to the lactobacillus surface instead of being secreted.
"A single bacteria would have many hundreds or perhaps
thousands of copies of CD4 on its surface," said Lewicki.
Montefiori believes it shouldn't be much of a problem to
develop the system. "I believe that we do have the molecules
that could be used in this system that would make it very
potent barrier," he said. There are already several very
effective antibodies against particular HIV strains available,
he points out. Seeding the vagina with bacteria that produce a
mixture of these antibodies could prove effective, he
suggests.
The researchers have already been working to see how
practical the bacteria will be as a clinical product. The
bacteria are cheap and easy to produce on a large scale.
Although the genetically engineered bacteria have not yet been
tested, unmodified Lactobacillus can colonize the
vagina effectively, says Lewicki, and persists for a period of
weeks.
"The ultimate vision would be that this would be a product
that a woman could use ... let's say once a week," he
suggested, noting that this would avoid many of the social
difficulties associated with current "on-the-spot" barrier
methods. | 
