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New Way To Disarm Staph Infections

April 16, 1998

WASHINGTON (AP) _ Scientists have discovered a protein that may help outwit one of the world’s toughest bacteria, offering the hope of a vaccine to avoid staph infections without causing dangerous drug resistance.

The work is still in very early stages, but 72 percent of mice vaccinated with the protein were protected against staph infections, report University of California, Davis, scientists in Friday’s edition of the journal Science.

``We desperately ... need innovative strategies to deal with staph infections,″ said Dr. Stephen Heyse of the National Institutes of Health, which awarded a biotechnology company $100,000 last month to begin work on the vaccine. ``This approach was quite novel and interesting.″

The discovery ``shows a lot of promise,″ added Harvard University microbiologist Jean Lee.

The protein is called RAP. When staph bacteria enter the body, they secrete RAP until enough is produced to set off a chain reaction that creates staph toxins. If the bacteria couldn’t produce enough RAP, the germs would be harmless, said Naomi Balaban, a UC Davis pathologist who discovered the protein.

Her idea: Use RAP as a vaccine, spurring the immune system to produce antibodies that would recognize the protein once staph bacteria began churning it out and would neutralize it. That would disarm staph before it causes serious infection.

And because a RAP vaccine wouldn’t kill the actual bacteria, as antibiotics do, it wouldn’t spur the bugs to mutate into drug-resistant forms that now threaten to become untreatable, Balaban added.

``The bacterium doesn’t realize it’s being jeopardized,″ she explained. ``No RAP, no toxins, no disease.″

Among bacteria, staphylococcus aureus causes the most disease, giving rise to everything from minor skin infections to life-threatening blood poisoning, pneumonia and wound infections. It is a particular threat in hospitals, infecting up to 500,000 hospitalized Americans every year.

Antibiotics are losing their effectiveness as more bacteria are exposed to the drugs and mutate to avoid them. Many strains of staph already are untreatable with standard drugs, and scientists were shocked to discover last summer that the germ is developing resistance to the antibiotic of last resort, vancomycin.

``Antibiotics are our medical miracles. The more we use them, the greater the chance we’re going to lose them,″ Dr. William Jarvis of the Centers for Disease Control and Prevention warned last week.

So scientists are furiously searching for new approaches, including vaccines that would prime the body to attack various bacteria directly. However, those attempts so far haven’t worked well.

Balaban’s discovery is sneakier, disarming staph germs instead of attempting to kill them.

She vaccinated mice with RAP purified from a strain of staph that causes skin lesions, and then exposed the mice to the staph germs.

All of the unvaccinated ``control″ mice became infected, but only 28 percent of the vaccinated mice did _ and they had 76 percent smaller skin lesions than the unvaccinated mice. Three percent of the vaccinated mice died from their infection, vs. 25 percent of untreated mice.

That’s not proof that a RAP vaccine would work, Harvard’s Lee cautioned. A skin infection is the easiest staph to overcome, so the real challenge is trying RAP against more life-threatening systemic staph infections, something Balaban plans to do.

And even if a vaccine eventually worked, at-risk people like the frequently hospitalized or health care workers would have to get it in advance of infection. So Balaban also is looking for a drug that would disarm staph once someone was sick. Her candidate is a RAP relative.

The biotech company Panorama Research Inc. is helping to develop Balaban’s research, but experiments in people are several years away.

Still, Balaban says her approach mimics how nature protects against staph: She recently tested cows and found that 80 percent of the animals who have never been sickened by staph naturally harbor antibodies that neutralize RAP _ while sick cows didn’t have that immune response.

``This approach may not necessarily replace antibiotics,″ she said. But ``it seems like anti-RAP antibodies are really important for protection.″

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