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Thorax. 2014 Jun;69(6):565-573. doi: 10.1136/thoraxjnl-2013-204605. Epub 2014 Jan 24.

A limited CpG-containing oligodeoxynucleotide therapy regimen induces sustained suppression of allergic airway inflammation in mice.

Author information

1
Dynavax Technologies, Berkeley, CA 94710.
2
Knowledge Synthesis, Berkeley, CA 94710.
3
Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London SW7 2AZ UK.
#
Contributed equally

Abstract

BACKGROUND:

CpG-containing oligodeoxynucleotides (CpG-ODNs) are potent inhibitors of T helper 2 mediated allergic airway disease in sensitised mice challenged with allergen. A single treatment has transient effects but a limited series of treatments has potential to achieve clinically meaningful sustained inhibition of allergic airway disease.

OBJECTIVE:

To optimise the treatment regimen for sustained efficacy and to determine the mechanisms of action in mice of an inhaled form of CpG-ODN being developed for human asthma treatment.

METHODS:

We set up a chronic allergic-asthma model using ragweed-sensitised mice exposed weekly to intranasal ragweed. Using this model, the effects of a limited series of weekly intranasal 1018 ISS (CpG-ODN; B-class) treatments were evaluated during treatment and for several weeks after treatments had stopped but weekly allergen exposures continued. Treatment efficacy was evaluated by measuring effects on lung T helper 2 cytokines and eosinophilia, and lung dendritic cell function and T-cell responses.

RESULTS:

Twelve intranasal 1018 ISS treatments induced significant suppression of bronchoalveolar lavage eosinophilia and interleukin 4, 5 and 13 levels. This suppression of allergic T helper 2 parameters was maintained through 13 weekly ragweed exposures administered after treatment cessation. Subsequent experiments demonstrated that at least five treatments were required for lasting suppression. Although CpG-ODN induced moderate T helper 1 responses, suppression of allergic airway disease did not require interferon γ but was associated with induction of a regulatory T-cell response.

CONCLUSIONS:

A short series of CpG-ODN treatments results in sustained suppression of allergic lung inflammation induced by a clinically relevant allergen.

KEYWORDS:

Allergic Lung Disease; Asthma; Asthma Pharmacology; Innate Immunity

PMID:
24464743
PMCID:
PMC4558941
DOI:
10.1136/thoraxjnl-2013-204605
[Indexed for MEDLINE]
Free PMC Article
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