For more than half a century, researchers have tried to create a vaccine against Group A streptococcus, the nasty infectious bacteria that cause strep throat and rheumatic fever - and kill up to half a million people a year in the developing world.
They might finally be on the right track. In a study published in today's issue of The Journal of the American Medical Association, scientists report that a new strep vaccine showed strong signs of working in humans and is also safe.
"This is an important first step," said the study's lead author, University of Maryland vaccine researcher Karen Kotloff.
Between 1999 and last year, she and her colleagues injected the vaccine into 28 healthy Baltimore-area adults. The medicine produced no serious health problems, and it triggered a large increase in antibodies to fight off the bacteria.
"It's a well-done, scientifically sound study," said Fran Rubin, a program officer at the National Institute of Allergy and Infectious Diseases (NIAID), which funded the work. "The vaccine strategy has promise."
Experts cautioned that the vaccine would require several more larger trials to confirm its safety and effectiveness, and it probably would not be available for five to 10 years.
Kotloff's study is the first human trial for any Group A strep vaccine in more than three decades. In 1969, two children involved in a strep vaccine study came down with rheumatic fever.
Although the cases were never definitively connected to the vaccine, some scientists suspect that the vaccine somehow triggered the fevers. The trial was stopped, and the U.S. Food and Drug Administration subsequently prohibited the sale of Group A strep vaccines.
In the aftermath, researchers realized that to develop a safe and effective vaccine, they needed to better understand the structure of the Group A strep bacteria. Over the past 10 years, this knowledge reached a point that scientists began again to develop vaccines.
"It took three decades to sort things out," said Dr. Michael Pichichero, a professor of microbiology and immunology at the University of Rochester. An expert on Group A strep, Pichichero wrote an editorial accompanying Kotloff's paper. He said her report "gives us great hope" that the new vaccine avoids the hazards of previous versions.
But Pichichero noted that Kotloff's study looked at a small number of adult subjects, some of whom had already been exposed to the Group A strep bacteria. The vaccine, by contrast, would likely be given to a very different population - children who had little or no exposure to strep. Researchers must establish that the vaccine is safe and effective for this group, he said.
The new version was developed by Dr. James Dale, an infectious disease specialist at the University of Tennessee Health Sciences Center and the Veterans Affairs Medical Center, both in Memphis.
He has spent the past 20 years working on the medication. He focused on "M proteins," parts of the bacterium that protect it from the body's defense system.
For decades, researchers have known that when separated from the bacterium itself, M proteins could boost the body's immune response. Then, when exposed to the actual bacteria, the body is prepared and kills the invaders before they get a foothold.
But some research has found that injecting these detached M proteins causes the antibodies to attack the body's own tissues, especially the heart, kidneys, joints and brain. This auto-immune response could have contributed to the rheumatic fever cases in the 1969 study.
To get around this potential hazard, Dale used genetic engineering to create an artificial version of the M proteins. These synthetic proteins contain only the region that stimulates the immune response to Group A strep, but not the piece that creates the auto-immune problems.
"This vaccine is without a doubt the most complex vaccine that's ever been introduced," said Dale, who also participated in the new study. Dale receives support from ID Biomedical Corp., a Canadian company that hopes eventually to sell the vaccine. Kotloff, the study's lead author, has no financial connection to the company.
In this country, Group A strep is generally a painful but ultimately benign ailment, which mostly afflicts children. Every year, more than 10 million children come down with the most common strep throat, according to the National Institutes of Health. Most cases are treated with a course of standard antibiotics. (Another kind of strep, Group B, mostly infects newborn babies.)
The bacteria are not always so benign: In rare cases, they cause rheumatic fever, toxic shock syndrome and necrotizing fasciitis, also known as flesh-eating disease. In 1990, for instance, an aggressive strep infection killed Muppets creator Jim Henson. About 8,000 people die in this country every year from strep-related causes.
In the developing world, the bacteria are much more deadly. In these regions, antibiotics are often too expensive, so the bacteria simply fester.