February 20, 2002
NICHD Scientists Develop Vaccine
Against Deadly Hospital-Acquired Infection
Scientists at the National Institute of Child Health and Human Development (NICHD)
and the biologics firm Nabi have developed the first vaccine against
Staphylococcus aureus, a major cause of infection and death among hospital
patients. The study appears in the February 14 New England Journal of
"Staphylococcus aureus bacteria can be life-threatening and are rapidly
growing resistant to the antibiotics used to treat them," said Duane
Alexander, M.D., director of the NICHD. "This new vaccine may provide a
powerful new way to prevent the thousands of serious S. aureus infections
that occur each year."
S. aureus is an opportunistic bacteria — infecting people whose immune
systems have been weakened, explained an author of the study, John Robbins,
M.D., chief of the NICHD's Laboratory of Developmental and Molecular
Immunity. S. aureus is a common cause of bacteremia-bacterial infection of
the bloodstream. Patients undergoing hemodialysis for end stage kidney
disease are particularly susceptible to S. aureus blood infection, with
nearly 3 percent developing the infection each year.
S. aureus infection causes illness ranging from minor skin infections to
life-threatening diseases such as severe pneumonia, meningitis, bone and
joint infections, and infections of the heart and bloodstream. Many strains
of S. aureus are resistant to methicillin, the antibiotic used to treat it.
Similarly, researchers have also discovered strains of the bacteria that are
resistant to the antibiotic vancomycin, the only antibiotic known to kill
methicillin-resistant S. aureus.
Dr. Robbins explained that the late Walter Karakawa, of Pennsylvania State
University, first made the critical discovery that S. aureus has capsular
polysaccharides — complex sugar molecules — in its outer covering, or
capsule. Dr. Karakawa, working with scientists at the NICHD; Willie Van of
the U.S. Food and Drug Administration; Jean-Michel Fournier of the Institute
Pasteur, in Paris; and Ali Fattom, then with NICHD, and now with Nabi,
conducted additional research on the organism.
In a series of experiments over the past 15 years, these researchers showed
that S. aureus had 13 capsular polysaccharides, only two of which, types 5
and 8, accounted for about 85 percent of polysaccharides isolated from the
blood of patients infected with the bacteria. These two polysaccharides
shielded S. aureus, preventing the white blood cells of the immune system
from recognizing it and targeting it for destruction.
The researchers knew that antibodies to these polysaccharides were capable
of killing the bacteria, but were confronted with a technical problem.
Without assistance, the immune system could not recognize the
polysaccharides, and so could not make antibodies against them. Antibodies
are immune system proteins that recognize a particular substance. Together
with another protein called complement, antibodies begin the first steps in
the complex sequences of events by which the immune system destroys
The researchers then chemically coupled the polysaccharides to a medically
useful protein to form a "conjugate." Tests in mice showed that this
conjugate approach allowed the immune system to produce antibodies that
could then inactivate the bacteria. Later testing showed that this approach
produced antibodies in healthy adults. Similarly, hemodialysis patients
produced low levels of the antibodies. The project was then transferred to
Nabi, under the direction of Dr. Fattom, another author of the paper. Dr.
Fattom showed that increasing the amount of the new vaccine given to
hemodialysis patients would allow them to produce higher levels of
Soon after, the NABI researchers conducted a double-blinded, randomized,
saline controlled trial of the vaccine. In this kind of trial, neither the
patients nor their physicians know who receives the vaccine or who receives
the placebo, in this case, a harmless salt solution.
From three to 40 weeks after the start of the trial, the vaccine reduced the
occurrence of bacteremia by 57 percent, with 11 bacteremias in the
vaccinated group (892 patients) and 26 in the control group (906 patients).
After the 40th week, this figure fell to 26 percent. In general, the authors
noted, antibody levels tend to decline rapidly in dialysis patients.
Dr. Robbins said that efforts to increase the efficacy of the vaccines will
include studies on the effectiveness of a booster dose of the vaccine given
one year later. In addition, researchers will target the vaccine to a newly
discovered polysaccharide type 336. This resulting new vaccine should allow
the immune systems of vaccinated patients to be able to recognize nearly 100
percent of S. aureus types found in blood infections.
"The conjugate vaccines were effective in hemodialysis patients who had
severely depressed immunity," Dr. Robbins said. "It is likely that the
vaccine will be more effective in individuals with less depressed immune
systems who are at risk for S. aureus infections, such as patients with
chest and cardiac surgery and with joint replacements."
Dr. Robbins and another author of the paper, Rachel Schneerson, M.D., had
earlier received the Pasteur and Lasker Awards for using the conjugate
approach to develop a vaccine that virtually eliminated disease caused by
the deadly and debilitating bacteria, Haemophilus influenzae type B (Hib),
from the developed world. (http://www.nichd.nih.gov/new/releases/cviawar2.cfm).
The NICHD is part of the National Institutes of Health, the biomedical
research arm of the federal government. The Institute sponsors research on
development, before and after birth; maternal, child, and family health;
reproductive biology and population issues; and medical rehabilitation.
NICHD publications, as well as information about the Institute, are
available from the NICHD Web site,
http://www.nichd.nih.gov, or from the NICHD Clearinghouse,
1-800-370-2943; e-mail NICHDClearinghouse@mail.nih.gov.
Source: National Institute of Health