HOPES of protecting people against some of the most dangerous sexually transmitted diseases have been boosted by the first test of a new method of immunisation. A team in Montana has immunised mice against Chlamydia, a bacterium that can cause infertility in women. The same approach might even work against HIV.
Until now, vaccines have been notoriously unsuccessful at stimulating immune responses in the mucous membranes ofthe body, the route through which HIV, Chlamydia and other sexually transmitted pathogens enter the body. And though vaccines are good at stimulating antibody-producing B cells, they are poor at triggering T cells to destroy infected cells. T cells are vital in the fight against Chlamydia and HIV.
So Harlan Caldwell and his colleagues at the Rocky Mountain Laboratory of the National Institute of Allergy and Infectious Diseases (NIAID) in Montana tried a different approach. They took bone marrow from female mice and cultured dendritic cells by adding interleukin-4. Dendritic cells recognise foreign molecules and recruit other cells of the immune system to attack invaders. The team added heat-killed Chlamydia to the culture to sensitise the dendritic cells to the bacterium and then put the cells back into mice.
This technique is already used against some cancers, where dendritic cells are sensitised to cells taken from the patients' own tumour. But this is the first time it has been used to immunise against infectious disease, says Caldwell.
When the immunised mice were later exposed to live Chlamydia, their response was as vigorous as that of mice immune to the disease because of a prior infection, and none developed signs of disease (The Journal of Experimental Medicine, vol 188, p 809). The dendritic cells triggered the appropriate immune response in the mucous membrane of the vagina, says Caldwell. Caldwell is optimistic that the technique will work in people. Some form of vaccination is badly needed, as a recent study of army recruits has suggested that rates of chlamydial infection among young women in the US are as high as 10 per cent (This Week, 12 September, p 5). A human version would rely on culturing dendritic cells from blood samples, rather than bone marrow (see Diagram). No clinical trails have yet begun, though a test in primates is already under way.
Some experts warn that the approach may be too expensive for mass use, however. "This would be a very complex way to vaccinate," says Robert Brunham, an infectious disease researcher at the University of Manitoba in Winnipeg.
But Caldwell says that his research may eventually lead to effective conventional vaccines. Until now, Chlamydia experts feared that the immune system would respond only to an active infection by live bacteria. Caldwell's experiments show that dead Chlamydia carry molecules on their surface that can provoke immunity. If researchers can identify those molecules, they should be able to develop a vaccine. "Now we can tear the system apart and hopefully develop more conventional ways to do it," says Caldwell.
But for a high-profile and deadly disease such as AIDS, even the unconventional approach may be worth the effort and expense. Several laboratories are already trying to use isolated dendritic cells to stimulate immunity to HIV, says Anthony Fauci, director of the NIAID, based at its headquarters near Washington DC. Caldwell's results prove that the concept works, he says.
Author: Bob Holmes
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