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The search for an effective syphilis vaccine has proven elusive. Progress has been limited, in part, because only five labs worldwide are studying Treponema pallidum, the organism that causes the disease. But the recent completion of mapping the bacterium's genome may provide researchers with the clues they need to develop an effective vaccine.
Dr. Sheila Lukehart, a microbiologist from the University of Washington in Seattle, reported at the 40th Interscience Conference on Anitmicrobial Agents & Chemotherapy on five molecules that slow the development of syphilis in animal models. The results are encouraging, but they are just a first step. None of the compounds completely prevents syphilis infection.
The World Health Organization estimates that more than 12 million new cases of syphilis occur worldwide each year. Most victims are in developing countries, and the heaviest burden is in Africa, where infection rates range from 10% to 30% of the population. Syphilis infection rates have been declining in the U.S. and Europe over recent years, but public-health experts still consider it a serious problem.
60 SHOTS. Syphilis results in open genital sores, providing an avenue of entry for many other sexually transmitted diseases, especially HIV. In addition to painful genital lesions, syphilis can lead to blindness, paralysis, and insanity. It's also transmissible from mother to child during pregnancy and nearly always results in the death of the developing infant.
It has been known for almost 30 years that a syphilis vaccine is theoretically possible. In 1973, Dr. James N. Miller of the University of California in Los Angeles showed that it was possible to inoculate rabbits with a weakened form of the bacterium and give them protection for at least a year. The problem was that achieving this level of immunity required 60 intravenous injections over the course of 37 weeks, a course of therapy that's too long and too invasive to be practical for people.
Today, Lukehart's compounds are among the promising keys to a vaccine identified to date. All three are proteins present on the surface of the syphilis bacterium, so they're easy targets for an attack by the immune system's killer cells. Her group discovered the targets by sifting through the syphilis bacterium's genome for proteins that, based on their sequences, were likely to be exposed on the germ's surface. Fifteen were identified in this search.
RAPID HEALING. To test the activities of candidate compounds, Lukehart's group first immunized rabbits with each of the individual proteins, and then a short time later infected them with a very high dose of syphilis bacteria. The researchers then watched the rabbits for development of telltale ugly red lesions. When rabbits were inoculated with proteins present on the surface of the deadly microbes, the rabbits formed lesions, but in 80% of the cases, the ulcers were much smaller and healed more rapidly than in unimmunized animals.
That finding could have important public-health consequences, says Lukehart. Even though a vaccine built from one of these proteins still won't truly protect an individual from infection, it could help to limit the spread of syphilis in the population, since the disease spreads primarily through bacteria oozing from open sores. Also, by shrinking the lesions, it should be possible to limit the spread of other sexually transmitted diseases.
By Ellen Licking at the ICAAC conference in Toronto Edited by Douglas Harbrecht
Copyright 2000, by The McGraw-Hill Companies Inc. All rights reserved.
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