"We're very excited about this," said Eduardo Martins, MD, vice-president for clinical development at Dynavax Technologies, the San Francisco-based company developing the Tolamba ragweed allergy vaccine. "There have been 14 research trials to date with different dosages, and although they've been small, trial after trial, we've had consistently good results like this for patients across the board."
This randomized placebo-controlled study — the largest to date on this ragweed vaccine — included 462 people aged 18 to 55 years with confirmed ragweed allergy. One group received 6 weekly injections of the vaccine in incremental doses; the other group received injected placebo. Patients were then followed for 2 allergy seasons and asked to electronically report their daily hayfever symptoms, medication use, and related factors.
Those who had received the vaccine experienced an average 21% decrease in nasal symptoms during 2004 and a 28.5% decrease during 2005. These patients also reported a 40% to 60% average reduction (years 1 and 2) in their use of fexofenadine and pseudoephedrine. Placebo-treated patients, however, reported increasing allergy symptoms scores during those 2 years and more medication use. No serious systemic effects were reported and local site reactions were mild to moderate.
"It's certainly interesting to us considering ragweed allergy is the most common in the United States," said session comoderator Myngoc Nguyen, MD, an allergy specialist at Oakland Medical Center in Oakland, California. "I think more research is appropriate to uncover the mechanisms of this treatment."
This experimental vaccine takes advantage of a trick that scientists learned from bacteria. Bacteria carry a specific DNA segment that triggers 2 immune responses when it recognizes a pathogenic invader. First, it triggers a highly protective immune response by bolstering T-helper 1 antibodies. Second, it suppresses the inflammation response — characteristic of miserable allergy symptoms — by suppressing T-helper 2 antibodies.
The vaccine contains a proprietary synthetic version of this bacterial-type DNA segment (known as immunostimulatory sequence, or ISS) that turns on this protective-but-noninflammatory immune response. a A high dose of the major ragweed allergen, known as Amb a-1, is covalently linked within a protective coating of ISS.
"Basically, we are using ISS to re-educate the immune system about how it should respond specifically to this allergen," Dr. Martins told Medscape. "Now the body recognizes the allergen as if it were a bacterial or viral pathogen and it generates a specific protective response instead of that nonspecific inflammatory response that makes this allergy so uncomfortable for patients.
"We've seen this work with the major ragweed allergen, and it's plausible that this ISS linking technology could work for other allergens as well," he said.
One theory is that an increase in immunoglobulin G (IgG) levels, which counter inflammation, may partly explain the vaccine's efficacy. In this study, Dr. Martins also showed that patients who had received the vaccine had a transient 2- to 3-fold increase in IgG levels compared with those given placebo. The vaccinated patients also tended to be protected against seasonal increase in IgE, unlike those treated with placebo.
Whether the vaccine could truly resolve allergy symptoms in America's 30 million hayfever sufferers remains to be seen, noted Dr. Nguyen.
"This vaccine contains the major allergen in ragweed, but there are others," she said. "We also wonder whether it's useful to have a single-allergen vaccine considering most people have multiple allergies. As always, more information is needed."
A 2-year multicenter, placebo-controlled trial is now underway in 738 adults with ragweed allergy. A 3-year pediatric study will also be completed in 2007. Company officials said they expect to file a biological license application for Tolamba with the US Food and Drug Administration in 2008.
ACAAI 2006 Annual Meeting: Abstract 21. Presented November 12, 2006
source - Medscape