Experimental Staph Vaccine Protects Rats

Researchers at Harvard Medical School (Boston) have developed a vaccine that protects mice against multiple strains of Staphylococcus aureus, an increasingly stubborn microbe and the most common cause of hospital-acquired infections. The new vaccine is the first to be made from a bacterial molecule produced primarily during infection, rather than in laboratory culture. A report of the study by scientists at Brigham and Women's Hospital (Boston) and Harvard Medical School appears in the May 28, 1999 issue of Science.

"This is an intriguing finding and a hopeful step against a very worrisome pathogen," says Anthony S. Fauci, director of the National Institute of Allergy and Infectious Dieseases, which funded the work. "Within the last two years, S. aureus has become increasingly resistant to antibiotics. Most troubling is the emergence of strains that are partially resistant to vancomycin, our last line of defense against this pathogen. New treatments and, ideally, an effective vaccine, are urgently needed."

Each year an estimated 500,000 patients in American hospitals contract staph infections. S. aureus, the chief culprit, also is a common source of community acquired infections, and causes illnesses that range from minor skin infections and abscesses to life-threatening diseases such as severe pneumonia, meningitis, bone and joint infections, and infections of the heart and bloodstream.

Molecules isolated from bacteria grown in the laboratory have been one source of new vaccine candidates. However, since bacterial growth under laboratory conditions may not mimic an actual infection, scientists recently have begun searching for bacterial products that are activated specifically during infection.

"Presumably, these products are critical for infection and disease progression, and would therefore be logical targets for new therapeutics or vaccines," explains Gerald B. Pier, who led the research team that developed the new vaccine.

The researchers found that although tissue from humans and mice infected with S. aureus contained a staph polysaccharide molecule known as PNSG (poly-N-succinyl Beta-1-6 glucosamine), few S. aureus strains produced PNSG when cultivated in the laboratory.

Pier and coworkers purified the elusive molecule and injected it into rabbits. The rabbits produced large amounts of PNSG antibodies that persisted for at least eight months. The researchers then injected the PNSG antibodies into mice and exposed them to eight different strains of S. aureus, including strains resistant to the antibiotic methicillin and partially resistant to vancomycin. None of the animals developed an infection.

"Our findings suggest that this vaccine has the potential to provide immunity to the multi-drug resistant S. aureus 'superbug' that we have heard alarming reports of in the last year or so," Pier says.

Pier and his colleagues note that in addition to S. aureus, other bacterial species classified as coagulase-negative staphylococci, or CoNS, also produce PNSG. "Together, S. aureus and CoNS account for 40% to 60% of bacterial blood isolates from hospitalized patients," says Pier. "Therefore, an additional potential advantage of a PNSG vaccine might be protection against the spectrum of clinically important CoNS." Pier adds that he and his colleagues hope to move the PNSG vaccine into human trials soon, but predicts that such trials are one to two years away. They currently are negotiating licensing rights for the vaccine.

For more information: Gerald B. Pier, Channing Laboratory, Harvard Medical School, 180 Longwood Ave., Boston, MA 02115. Tel: 617-432-2269. Fax: 617-731-1541. Email: gpier@warren.med.harvard.edu.