Gains cited in quest for strep vaccine
The 70-year hunt for a vaccine against strep throat and its potentially lethal complications has reached a milestone, as scientists report today that a novel inoculation armed the immune systems of adult volunteers to fight the infection without spawning serious side effects.
The vaccine melds harmless bits of protein from six strains of group A streptococcal bacteria, the source of the sore throats that sideline millions of schoolchildren each year. In a University of Maryland study, 28 adults received three immunizations each over a period of up to four months, and laboratory tests showed that the shots spurred the immune system to generate disease-fighting cells targeted against these six strains. Future studies will try to prove that the inoculation actually prevents disease.
The study was small, and it could be a decade or longer before a strep vaccine becomes widely available, but the report in the Journal of the American Medical Association provides the best hope yet to parents in the United States that their children may some day get a shot of protection against one of the most common illnesses of childhood.
In the developing world, the implications could be even more dramatic: Global health studies have documented up to 20 million cases of heart damage related to the strep bacteria, with 400,000 deaths annually. Strep infections can start with a sore throat before progressing to rheumatic fever and, ultimately, a deadly heart condition.
''What would a vaccine do? Potentially in the United States, it could decrease doctor visits, it could decrease use of antibiotics," said microbiologist Fran Rubin, a program officer at the National Institute of Allergy and Infectious Diseases, a federal agency that helped to pay for the study. ''In the developing world, there's a far more significant impact in terms of public health. The hope is that we could prevent rheumatic heart disease and save lives."
Vaccine and infectious disease specialists hailed the findings as encouraging, but they stressed that the results are preliminary and that the inoculation needs to be tested more widely.
''What these folks have done is really quite masterful," said Dr. Harris Berman, dean of public health at Tufts University School of Medicine. ''The part we need to be cautious about is that it's a long way from this study of 28 adults to having a commercially available vaccine worldwide for use on children."
The quest to develop a shot against strep has been marked by frustration and scientific missteps, which led regulators to make increasingly stringent demands that researchers conclusively demonstrate that any vaccine against the germ prevents disease while not inflicting unintended harm.
The earliest efforts to engineer a strep vaccine can be traced to the 1930s. Researchers focused on something called an M protein, which resides on the surface of the bacteria. Scientists recognized that the M protein was like a bullfighter's cape waved in front of the human immune system, prompting it to respond with vigor.
But it turned out that the M protein was a two-faced agent: While it could cause the immune system to respond appropriately to invading germs, it could also result in dangerous side effects.
Trials of an M protein vaccine in the 1970s, for example, ended in some children coming down with the very complications the shot was meant to prevent, including rheumatic fever. And that trial embraced practices now shunned by vaccine researchers: Some of the children got weekly vaccinations for a year, a frequency that scientists would never entertain today.
''It was not known for certain whether the vaccine had anything to do with those cases of rheumatic fever, but it raised concerns and put a damper on the development of a vaccine," said Dr. Karen L. Kotloff, who presided over the new vaccine trial.
Still, a cadre of scientists persisted, determined to separate the good parts of the M protein from the bad. Dr. James B. Dale at the University of Tennessee in Memphis championed those efforts and eventually identified the sections of the protein that generated the right kind of immune response.
''What Jim Dale saw," Kotloff said, ''was that you could take the tip of the M protein and that was a good guy and it didn't have any bad regions."
Then, working with a Canadian biotech company named
Studies have estimated that more than 100 different types of the germ are in circulation around the globe.
''Any pathogen that has many, many different subtypes is a real headache for researchers," said Dr. Shan Lu, a vaccine scientist at the University of Massachusetts Medical School in Worcester.
ID Biomedical has already begun a trial in Canada of a shot meant to guard against 27 types of group A strep, and the company's chief executive officer, Dr. Anthony Holler, said yesterday that vaccine stimulates an immune system response against strains responsible for 85 percent of the illness associated with the germ.
In addition to strep throat and its complications, the bacteria are responsible for rarer and, often, more fatal conditions such as necrotizing fasciitis -- better known as flesh-eating bacteria -- and toxic shock syndrome.
In an editorial accompanying the study in the medical journal, Dr. Michael E. Pichichero of the University of Rochester Medical Center forecasts that studies enrolling 10,000 to 60,000 children will need to be performed before federal regulators will be willing to give their stamp of approval to a strep vaccine using the M protein. Holler said he expects to begin trials in children early next year.
At Catherine Bromberg's home in West Newton, the strep germ has been a frequent visitor. All three children, along with their parents, have been beset by sore throat and fever. The result: missed days of school and work. ''Everyone in the household is wandering around feeling miserable," Bromberg said.
So if a vaccine becomes available, Bromberg said, her children will probably be rolling up their sleeves.
''I would really consider having my kids vaccinated if the science were there," she said. ''Right now, we have decent methods for treating strep throat, but nobody wants to have your kids on antibiotics multiple times every single year."
Stephen Smith can be reached at stsmith@globe.com.
