Article Text

PDF

Original article
A limited CpG-containing oligodeoxynucleotide therapy regimen induces sustained suppression of allergic airway inflammation in mice
  1. John D Campbell1,
  2. Sariah A Kell1,
  3. Heather M Kozy1,
  4. Jeremy A Lum1,
  5. Rosemary Sweetwood1,
  6. Mabel Chu1,
  7. Cameron R Cunningham1,
  8. Hugh Salamon2,
  9. Clare M Lloyd3,
  10. Robert L Coffman1,
  11. Edith M Hessel1
  1. 1Dynavax Technologies, Berkeley, California, USA
  2. 2Knowledge Synthesis, Berkeley, California, USA
  3. 3Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK
  1. Correspondence to Dr John D Campbell, Dynavax Technologies, 2929 7th St, Ste 100, Berkeley, CA 94710, USA; dcampbell{at}dynavax.com

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.

  • Allergic Lung Disease
  • Asthma
  • Asthma Pharmacology
  • Innate Immunity
View Full Text

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Files in this Data Supplement:

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Airwaves
    Andrew Bush Ian Pavord