Millions of miserable, sneezing, itching, nose-blowing hay fever sufferers could find a strand of hope in a DNA-based vaccine developed by Johns Hopkins scientists, who say it appears to squelch the body's allergic response to ragweed pollen.
A small but promising study reported in today's New England Journal of Medicine says test subjects who had just six weekly injections of the vaccine - a fusion of bacterial DNA and ragweed protein - enjoyed a 60 percent reduction in allergy symptoms compared with people who got a placebo.
And the relief lasted through at least two full Baltimore ragweed seasons.
For Robert Campbell, 47, of Dundalk, an allergy sufferer who signed up for the study, the change has been extraordinary.
"I grew up in northern Baltimore County on a farm, and it [hay fever] has bothered me all my life," he said. "All hours of the day and night, sneezing and coughing. ... I normally try to avoid the outside."
But after six shots in 2001, he has stopped taking allergy medicines and has been symptom-free through six ragweed seasons, he said. "And I've taken up golf."
The results are preliminary. Only 25 people took part in the study, and only 14 of those actually received the vaccine.
But Dr. Peter S. Creticos, the lead investigator and medical director of the Johns Hopkins Asthma and Allergy Center in Baltimore, said the findings hold important promise for hay fever sufferers - and potentially for victims of other chronic inflammatory diseases, such as arthritis or gastrointestinal disorders.
"Ragweed is a nuisance for a significant number of people," Creticos said. But the immune system mechanisms that the vaccine tackles "can now be manipulated in our favor, and maybe we can use this to look at a whole variety of inflammatory diseases. That's the real promise here."
Dr. Marshall Plaut, chief of the allergic mechanisms section at the National Institute of Allergy and Infectious Diseases (NIAID), cautioned that the significance of the Hopkins study was limited by its small size and the vaccine's failure to affect the primary immune system response it was designed to look for - leakage of fluids from the blood vessels into the nose.
But the test subjects found relief anyway, he said, and the experiment, for the first time, proved that this DNA technology can have a clinically important impact on the immune system and allergic diseases.
"The magnitude of the effects are really impressive," he said, as was the fact that the test subjects were still happy two ragweed seasons after treatment.
The technology's promise for fighting other inflammatory diseases is less clear, Plaut said.
"Yes, one would hope to go beyond a single allergen in ragweed," he said. But "we're not so sure what proteins or other molecules are involved in these other diseases."
It's also not likely that inflammatory bowel disease or arthritis would respond to the same sort of manipulation of the immune system, he said.
About 40 million Americans suffer from seasonal allergies, and ragweed is considered the worst offender in North America. The ragweed season in Baltimore lasts from mid-August to October, and this season seems especially bad.
"People at work who normally don't have a problem, they've had problems this year," Campbell said.
But his own ragweed allergy has vanished. "I just wish they had something for the things I'm allergic to in the springtime," he said.
Most hay fever sufferers dread the season when their tormenters blossom. Pollen from the flowering parts of trees, grass, ragweed and other greenery triggers an unwanted cascade of allergic reactions - ranging from itchy, watery eyes, runny nose, sneezing and coughing to a sore throat or asthma attacks.
It's a runaway reaction from the body's immune system as it tries to rid the respiratory tract of the invasive threat it perceives from the inhaled pollen's proteins.
Until time or frost ends the onslaught, most victims muddle through with handkerchiefs, over-the-counter or prescription antihistamines and nasal sprays, all designed to suppress their symptoms.
If those don't work, some turn to allergists.
After conducting skin tests to pinpoint the specific irritant that's triggering their symptoms, physicians begin a series of injections. These shots actually contain small amounts of the offending allergen, which the immune system, over time, learns to tolerate.
Unfortunately, a course of allergen immunotherapy typically requires one or two allergy shots per week for six months, followed by one or two shots a month for three to five years, Creticos said. It can cost thousands of dollars, but it works.
"In time, the allergy injections begin to shut off that chronic inflammation," he said. "It quiets the process. But it takes years to do it."
The experimental, DNA-based vaccine appears to do just as well with just six weekly injections. "And it lasts, hopefully, for years," he said. It should also be cheaper.
For their study, Creticos and his team injected 11 test subjects with inactive placebos. Fourteen received a vaccine containing a strand of DNA derived from a bacterium, fused chemically to the most allergenic portion of the ragweed pollen protein.
The vaccine was provided by Dynavax Technologies Corp. of Berkeley, Calif. The study was funded by the NAIAD and the Juvenile Diabetes Research Foundation.
Investigators at the University of California, San Diego have shown that the bacterial DNA can shut down the production of IgE antibodies - a key sequence in the body's inflammatory response.
At the same time, it stimulates other immune cells, called cytokines, that moderate the response.
Bottom line: The drug tweaks the immune system to produce a more normal response to pollen protein, without significant side effects.
Test subjects, who ranged in age from 23 to 60, kept symptom diaries. They reported 60 percent less sneezing, nasal congestion, runny nose, postnasal drip and itching of the eyes, ears, nose and throat than the placebo group.
A commercial product is still years away.
Creticos said his team recently completed part of a multicenter, Phase 3 clinical trial of the DNA vaccine, with about 400 test subjects.
Further studies, which will start in 2007 or 2008, could eventually lead to drug approval by the U.S. Food and Drug Administration.