Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-32661

Senti, G; Johansen, P; Haug, Susanne; Bull, C; Gottschaller, C; Müller, P; Pfister, T; Maurer, P; Bachmann, M F; Graf, N; Kündig, T M (2009). Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial. Clinical and Experimental Allergy, 39(4):562-570.

[img] PDF - Registered users only
1MB

View at publisher

Abstract

BACKGROUND: B-type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half-life, which is due to its phosphorothioate backbone. A-type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus-like particles (VLP) consisting of the bacteriophage Qbeta coat protein, A-type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A-type CpGs in humans. OBJECTIVE: To test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients. METHODS: A single centre, open-label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty-one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end-points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen-specific IgG and IgE. RESULTS: QbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom-free and this amelioration lasted for at least 38 weeks post-treatment. Following injections of QbG10 and HDM allergen extract, allergen-specific IgG increased, while there was a transient increase in allergen-specific IgE titres. Skin reactivity to HDM was reduced. CONCLUSION: The subcutaneous application of HDM allergen, together with A-type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo-controlled phase II studies.

Citations

63 citations in Web of Science®
69 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

2 downloads since deposited on 03 Mar 2010
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Medical Research
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:April 2009
Deposited On:03 Mar 2010 07:00
Last Modified:04 Sep 2014 10:06
Publisher:Wiley-Blackwell
ISSN:0954-7894
Publisher DOI:10.1111/j.1365-2222.2008.03191.x
PubMed ID:19226280

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page