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Previous Volume 355:1445-1455 October 5, 2006 Number 14 Next

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ABSTRACT

Background Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses.

Methods We conducted a randomized, double-blind, placebo-controlled phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen, conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients received six weekly injections of the AIC or placebo vaccine before the first ragweed season and were monitored during the next two ragweed seasons.

Results There was no pattern of vaccine-associated systemic reactions or clinically significant laboratory abnormalities. AIC did not alter the primary end point, the vascular permeability response (measured by the albumin level in nasal-lavage fluid) to nasal provocation. During the first ragweed season, the AIC group had better peak-season rhinitis scores on the visual-analogue scale (P=0.006), peak-season daily nasal symptom diary scores (P=0.02), and midseason overall quality-of-life scores (P=0.05) than the placebo group. AIC induced a transient increase in Amb a 1–specific IgG antibody but suppressed the seasonal increase in Amb a 1–specific IgE antibody. A reduction in the number of interleukin-4–positive basophils in AIC-treated patients correlated with lower rhinitis visual-analogue scores (r=0.49, P=0.03). Clinical benefits of AIC were again observed in the subsequent ragweed season, with improvements over placebo in peak-season rhinitis visual-analogue scores (P=0.02) and peak-season daily nasal symptom diary scores (P=0.02). The seasonal specific IgE antibody response was again suppressed, with no significant change in IgE antibody titer during the ragweed season (P=0.19).

Conclusions In this pilot study, a 6-week regimen of the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis. (ClinicalTrials.gov number, NCT00346086 [ClinicalTrials.gov] .)

Source Information

From the Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore (P.S.C., J.T.S., R.G.H., S.L.B.-W., A.P.K.); the Emmes Corporation, Rockville, MD (R.L.); the Institute for Asthma and Allergy, Wheaton, VA (H.L.); Dynavax Technologies, Berkeley, CA (R.C., J.J.E.); the Immune Tolerance Network, San Francisco (V.S.); and the Department of Medicine, Section of Allergy and Immunology, University of California, San Diego, San Diego (D.B.).

Address reprint requests to Dr. Creticos at the Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Cir., Baltimore, MD 21224, or at pcretic{at}jhmi.edu.

Full Text of this Article

Related Letters:

Immunotherapy with a Ragweed Vaccine
Seymour S. M., Chowdhury B. A., Simons F. E. R., HayGlass K. T., Creticos P. S., Schroeder J. T., Broide D.
Extract | Full Text | PDF  
N Engl J Med 2007; 356:86-87, Jan 4, 2007. Correspondence

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