Presented at:
58th AAAAI, New York, March 1-3, 2002
J Allergy Clin Immunol 109:743-4, 2002
Immunotherapy with immunostimulatory oligonucleotides linked to purified ragweed amb a 1 allergen: Effects on antibody production, nasal allergen provocation, and ragweed seasonal rhinitis
Creticos PS, Eiden JJ, Broide D H, Balcer-Whaley, SL, Schroeder, JT, Khattignavong, A, Li H, Norman P, Hamilton, R.
Johns Hopkins University, Dynavax Technologies Corp, and University of CA-San Diego
We have previously reported that linkage of a highly active immuno-stimulatory
phosphorothioate oligodeoxyribonucleotide (Dynavax 1018 ISS) with the
principal allergenic moiety of ragweed (Amb a 1) possessed significantly
reduced allergenicity [185 fold less reactive than licensed ragweed by
both quantitative intradermal skin test titration and BHR] and yet maintained
immunogenicity [induction of IgG anti-Amb a 1 antibody comparable to standard
immunotherapy]. We now report an exploratory, placebo-controlled, randomized,
investigator-blinded, clinical study in ragweed allergic adults that employed
a 6 injection treatment (tx) regimen to a target dose of 12 µg of
AIC (Amb a 1 - ISS conjugate). Our study included 25 patients [10 M. 15F];
mean age: 39 years; range of puncture skin test sensitivity to ragweed:
47-98 mm (mn: 71 mm). Study participants were evaluated for safety, tolerability,
and response to ragweed nasal challenge before and after study injections.
Subjects were also followed for immune response and clinical symptoms
during the ragweed season. Preliminary analysis indicated that study injections
were well tolerated. An analysis of antibody response in the two study
groups (grp) provided the following descriptive data [this includes all
19 subjects who completed the treatment phase of the study regardless
of final dose level achieved]: ? A rise in IgG anti-Amb a 1 (mean) was
observed in the AIC grp as contrasted to the placebo grp: AIC: baseline:
226 U/ml (med:163) vs post treatment: 519 U/ml (median:270); Placebo:
baseline: 428 U/ml (med:203) vs post treatment: 399 U/ml (med:205). ?
A modest rise in IgE anti-Amb a 1 (mean) was observed in the AIC group
as contrasted to the placebo group: AIC: baseline: 101 U/ml (med:41) vs
post treatment: 164 U/ml (median:77); Placebo: baseline: 85 U/ml (med:35)
vs post treatment: 58 U/ml (med:25). ? No rise in total IgE was observed
in either treatment group over the course of the treatment period [baseline
vs post treatment]. At the AAAAI session we will present the result of
testing of group differences in these three outcomes, a detailed analysis
of antibody measurements, T cell studies, nasal challenge parameters (cytokines/mediators),
nasal scraping cellular response, and clinical endpoints from the seasonal
symptom/medication and adverse event diaries. This research was performed
as a project of the Immune Tolerance Network, supported by the National
Institute of Allergy and Infectious Diseases, the National Institute of
Diabetes and Digestive and Kidney Diseases, and the Juvenile Diabetes
Research Foundation.