Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis

Peter S. Creticos, John T. Schroeder, Robert G. Hamilton, Susan L. Balcer-Whaley, Arouna P. Khattignavong, Robert Lindblad, Henry Li, Robert Coffman, Vicki Seyfert, Joseph J. Eiden, David Broide

Research output: Contribution to journalArticlepeer-review

472 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1445-1455
Number of pages11
JournalNew England Journal of Medicine
Issue number14
StatePublished - Oct 5 2006

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis'. Together they form a unique fingerprint.

Cite this