Rhinitis, sinusitis, and ocular diseasesSelective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA
Section snippets
Methods
This randomized, third party–blinded, placebo-controlled Phase I investigation was approved by the University of Manitoba Research Ethics Board, and written informed consent was obtained from all participants. The study was conducted entirely in midwinter, when there was no exposure to ragweed or other pollens. Individuals received 6 injections of investigational vaccine or placebo administered at weekly intervals (Fig 1).
Results
The AIC and placebo groups were demographically and clinically similar (AIC [n = 9]: 4 men, 41 ± 13 y, 76 ± 20 kg; placebo [n = 10]: 6 men, 41 ± 13 y, 79 ± 18 kg). They did not differ significantly in the intensity of cytokine and chemokine production or in the balance between their TH1 and TH2 immunity at preinjection baseline (P > .05); however, when ragweed-specific responses were evaluated 2 and 16 weeks after the sixth and last injection, the individuals in the AIC group exhibited striking
Discussion
In this proof-of-concept study of a novel approach to immune modulation in humans, we determined the effect of AIC on ongoing immunoregulatory responses and investigated its safety. We demonstrated for the first time that human systemic in vivo TH2 cytokine and chemokine ragweed-specific recall responses and IL-5, CCL17, and CCL22 levels readily detectable 6 months after the end of the ragweed season were markedly reduced after AIC, but not placebo, injections. In some individuals, reductions
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Supported by Dynavax Technologies Corp, the Canadian Institutes of Health Research, and the Canada Research Chairs Program. F. E. R. Simons, Y. Shikishima, and K. T. HayGlass have no competing financial interests. G. van Nest and J. J. Eiden are associated with Dynavax Technologies Corp.