Researchers at The Johns Hopkins University School of Medicine have successfully used an experimental DNA-based vaccine to protect against ragweed allergies, commonly known as hay fever, after just six injections. Patients receiving the vaccine showed an average 60 percent reduction in allergy symptoms compared to those receiving a placebo.
The experimental therapy holds the promise of one day eliminating the need for traditional allergy medicines targeting allergy symptoms, such as nasal steroids and antihistamines, and providing a safer, faster replacement for immunotherapy regimens, which are costly and take years to work, the researchers say.
The Hopkins study, conducted during two fall ragweed ("hay fever" ) seasons in Baltimore, Md., enrolled 25 volunteers, ages 23 to 60, with a demonstrated history of ragweed allergy. Fourteen people received the vaccine, administered as six weekly shots, while 11 others received placebo injections.
During the test period, allergic symptoms were monitored and recorded, right down to how often volunteers' noses ran and how many times they sneezed. Compared to the placebo group, those who received the vaccine exhibited a 60 percent reduction in all of their allergy symptoms, including sneezing, runny nose, watery eyes and itching.
Relief from allergic symptoms was as pronounced in the second year as in the first, even though no more vaccine was administered. Lead investigator Peter Creticos, M.D., medical director of the Johns Hopkins Asthma and Allergy Center in Baltimore, explained that such prolonged relief is an important part of his team's findings because it appears that the vaccine's efficacy doesn't wear off quickly. A new study, currently under way, will further examine the drug's lasting effects in a larger group of participants.
"This therapeutic intervention heralds a major advance in the treatment of allergic rhinitis," says Creticos. "Long-lasting relief can be achieved with a concise, six-week injection regimen, as opposed to the current, tedious, four- to five-year course of treatment with allergen immunotherapy."
Investigators at the University of California, San Diego (UCSD) had previously observed that a particular sequence of DNA, derived from bacteria, shuts down a T-helper cell (Th2) involved in the body's inflammatory response. Creticos and his team, recognizing that allergic disease is driven by Th2 inflammation, then embarked on a series of studies to evaluate the effectiveness of using this approach to treat allergies. The central question that they sought to answer was, What would happen if the DNA strand was linked to the most allergenic portion of the ragweed pollen protein, which is the number one cause of seasonal allergies in North America?
Dynavax Technologies Corp., of Berkeley, Calif., developed the vaccine and funded several of Creticos' early safety studies. Creticos was a paid consultant of Dynavax during that period. The current study was sponsored by the Immune Tolerance Network, which receives its funding from the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases.
Creticos explained that the vaccine works in two ways: by suppressing acute allergic reactions (like sneezing) and by helping the body better regulate chronic inflammation (like itchy eyes and a runny nose).
It is thought that the vaccine lessens the immune system's excessive reactions to inhaled allergens by stimulating protective cells that turn off the Th2 helper cells. The TH2 helper cells send out signals for the body to create more IgE, the protein largely responsible for making allergy sufferers miserable throughout the entire ragweed season. Someone allergic to ragweed has inherited the ability to make too much IgE antibody when exposed to inhaled allergens.
Additionally, the vaccine may activate specialized immune cells known as "dendritic cells" that serve as peacekeepers, maintaining balance by keeping inflammation in check over the long term and breaking an otherwise self-sustaining allergic cycle Creticos calls "Th2 orchestrated allergic inflammation."
"We are turning off an inappropriate or abnormal allergic response and returning the body to normalcy," says Creticos. "Our hope is that we can one day provide a long-term cure for hay fever and other chronic inflammatory diseases."
Creticos' current findings are published in the Oct. 5 issue of the New England Journal of Medicine.
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