Hay Fever Vaccine Nothing to Sneeze At

BALTIMORE, Oct. 4 -- An investigational hay fever vaccine it appears to ease the symptoms of ragweed allergy for up to two years after a course of only six injections, according to researchers here.

In a small, prospective randomized study, the vaccine reduced hay fever symptoms by about 60% compared with placebo, reported Peter Creticos, M.D., of Johns Hopkins, and colleagues, in the Oct. 5 issue of the New England Journal of Medicine. The effect lasted through two allergy seasons.

On the other hand, the vaccine had no effect on the nasal permeability response -- part of the inflammatory response to allergens -- when volunteers were challenged with ragweed allergens,

"This therapeutic intervention heralds a major advance in the treatment of allergic rhinitis," Dr. Creticos said. "Long-lasting relief can be achieved with a concise, six-week injection regimen, as opposed to the current four- to five-year course of treatment with allergen immunotherapy."

"We're not just treating the symptoms, we're targeting the fundamental defects in the immune system that cause allergy," he said.

The vaccine combines the key ragweed allergen (Amb a1) with a segment of DNA that binds to toll-like receptor 9. The interaction of the DNA and the receptor is associated with the inhibition of immune responses mediated by type 2 helper T (Th2) cells, the researchers noted.

The vaccine, dubbed AIC, is manufactured by Dynavax Technologies Corp. of Berkeley, Calif., which financed several of the preclinical and safety studies of the drug. Dr. Creticos was a consultant for the company at the time.

The current study was sponsored by the Immune Tolerance Network, an international collaboration of researchers based at the University of California San Francisco, and was financed by the National Institute of Allergy and Infectious Diseases.

The researchers enrolled 25 volunteers with a ragweed allergy and randomized them to the vaccine or placebo injections. They were followed through two ragweed seasons, although several participants dropped out or were lost to follow-up.

The primary endpoint was the nasal permeability response, as measured by albumin levels after a ragweed challenge and a nasal lavage, Dr. Creticos and colleagues said, but they found no significant change from baseline values.

However, the study found that during the first ragweed season:

• Compared with the nine volunteers getting placebo, the 10 getting vaccine had better peak-season rhinitis scores, peak-season daily nasal symptom diary scores, and midseason overall quality-of-life scores. The differences from placebo was significant at P=0.006, P=0.02, and P=0.05, respectively.
• The vaccine induced a transient increase in Amb a1-specific IgG antibody at the time of the injections, but suppressed the seasonal increase in Amb a1-specific IgE antibody.

During the second ragweed season, 15 patients remained in the study (six in the vaccine arm). Again, there were significant improvements over placebo in peak-season rhinitis scores and peak-season daily nasal symptom diary scores (at P=0.02 for both). The seasonal specific IgE antibody response was again suppressed.

The vaccine appeared to be safe and well-tolerated, Dr. Creticos and colleagues said, with the main adverse effects being self-limiting local injection site reactions.

"Although the mechanisms underlying the clinical benefit require further investigation, AIC vaccine has properties that make it qualitatively superior to standard allergen immunotherapy," wrote the authors.

The study's limitations, the researchers said, include its size, the lack of effect on the nasal permeability response, and the absence of long-term safety data on the vaccine.

A larger phase III trial is needed to confirm the results and determine the role of AIC as a therapeutic option in ragweed-induced allergic disease, Dr. Creticos and colleagues said.