Researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID) have developed a vaccine that protects mice against multiple strains of Staphylococcus aureus (S. 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 and Harvard Medical School in Boston appears in the May 28, 1999, issue of Science.
"This is an intriguing finding and a hopeful step against a very worrisome pathogen," says NIAID Director Anthony S. Fauci, M.D. "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 S. aureus. 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, Ph.D., who led the research team that developed the new S. aureus 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.
Dr. Pier and his colleagues 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," says Dr. Pier.
"I think this work has a very good chance of being a major advance," says Stephen Heyse, M.D., medical bacteriology and antibacterial resistance program officer at NIAID. "It looks like a great vaccine candidate for Staphylococci, in general, both S. aureus and S. epidermidis."
Dr. 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 percent to 60 percent of bacterial blood isolates from hospitalized patients," says Dr. Pier. "Therefore, an additional potential advantage of a PNSG vaccine might be protection against the spectrum of clinically important CoNS."
Dr. 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.
Other Ongoing NIAID S. Aureus Research
NIAID recently awarded a seven-year contract to MRL Pharmaceutical Services of Herndon, Va., to establish a network for tracking antibiotic resistance in S. aureus. The Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) is designed to enhance communication and collaboration among all investigators, from basic scientists to clinicians, studying this problem. To that end, the NARSA contractor will: develop an Internet Web site and electronic bulletin board; evaluate and compare methods for testing antibiotic susceptibility; and establish a repository of antibiotic-resistant S. aureus isolates for distribution to NARSA investigators, among other tasks.
NIAID supports ongoing projects to sequence the genomes of two S. aureus strains. Researchers at The Institute for Genomic Research in Rockville, Md., are sequencing a methicillin-resistant strain while a research team at the Oklahoma University Health Science Center is sequencing a strain that remains sensitive to antibiotics. These projects should help scientists identify S. aureus genes involved in the development of antibiotic resistance.
NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
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