Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 106, Issue 1, Pages 124-134Publisher
MOSBY-ELSEVIER
DOI: 10.1067/mai.2000.107927
Keywords
allergen-ISS conjugate; immunotherapy; immunostimulatory DNA sequence; CpG motifs; basophil histamine release; ragweed allergy
Categories
Funding
- NIAID NIH HHS [AI40682] Funding Source: Medline
Ask authors/readers for more resources
Background: Allergen immunotherapy is inconvenient and associated with the risk of anaphylaxis. Efforts to improve the safety of immunotherapy by means of chemical modification of allergens have not been successful because it greatly reduced their antigenicity. Recently, immunostimulatory DNA sequences (ISS or CpG motifs) have been shown to act as strong T(H)1 response-inducing adjuvants. Objective: We sought to determine whether conjugation of ISS to the major short ragweed allergen Amb a 1 results in enhanced immunotherapeutic potential in mice and decreased allergenicity in human subjects. Methods: A 22-mer ISS oligodeoxynucleotide (ISS-ODN) was coupled to Amb a 1 and used for immunization of mice, rabbits, and monkeys. Results: In mice the Amb a I-ISS conjugate induced a T(H)1 response (IFN-gamma secretion), whereas Amb a 1 induced a T(H)2 response (IL-5 secretion). The T(H)1 response was not observed with an Amb a I-non-ISS conjugate. Coinjection of Amb a 1 with ISS-ODN was much less effective in inducing a T(H)1 response. In mice primed for a T(H)2 response, injection with Amb a I-ISS conjugate induced a de novo T(H)1 response and suppressed IgE antibody formation after challenge with Amb a 1. Amb a 1-ISS conjugate induced high-titer anti-Amb al IgG antibodies in rabbits and cynomolgus monkeys, whereas Amb a 1 alone or Amb a 1 coinjected with ISS-ODN did not induce a detectable response. Amb a I-ISS conjugate was less allergenic than Amb a 1 alone, as shown by a 30-fold lower histamine release from human basophils of patients with ragweed allergy, whereas mixing ISS-ODN with Amb a 1 did not reduce histamine release. Conclusion: Amb a 1-ISS conjugate has an enhanced T(H)1-biased immunogenicity and reduced allergenicity. It may offer a more effective and safer approach for allergen immunotherapy than currently available methods.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available