Abstract
Background: Immunotherapy has gradually fallen out of favor for the treatment of many allergic diseases because of the overall convenience, safety, and efficacy of medications. However, investigations suggest that allergen/immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) conjugates (AICs) might have improved safety and efficacy compared with allergen extracts. Objective: We determined whether changes in the ISS-ODN conjugation ratio would effect the immunogenicity and allergenicity of AIC. Methods: Immunogenicity was determined by means of AIC vaccination of mice, followed by analysis of antigen-specific antibody and cytokine responses. The allergenicity of AIC was determined in mast cell release studies and in murine models of anaphylaxis and the Arthus reaction. Results: AIC induced a stronger immune response than allergen alone or allergen mixed with ISS-ODN, but higher-level ISS-ODN conjugation reduced its immunogenicity modestly. In mast cell degranulation studies AIC was approximately 100-fold less allergenic than native allergen, with stepwise increases in the ODN conjugation ratio leading to stepwise decreases in allergenicity. In anaphylaxis studies death rates were reduced from 100% with native allergen challenge to as low as 0% with high-ratio ISS-ODN AIC challenge. Similar results were obtained in an Arthus reaction model. Conclusion: These investigations establish that AIC is both significantly more immunogenic and less allergenic than native allergens and the techniques used might have further utility for the standardization and optimization of AIC formulations for use in allergic patients.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 413-420 |
| Number of pages | 8 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 110 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2002 |
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Keywords
- Anaphylaxis
- CpG motif immunotherapy
- Immunostimulatory DNA
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity. / Horner, Anthony A.; Takabayashi, Kenji; Beck, Lucinda; Sharma, Bhavya; Zubeldia, Jose; Baird, Stephen; Tuck, Stephan; Libet, Lev; Spiegelberg, Hans L.; Liu, Fu-Tong; Raz, Eyal.
In: Journal of Allergy and Clinical Immunology, Vol. 110, No. 3, 09.2002, p. 413-420.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity
AU - Horner, Anthony A.
AU - Takabayashi, Kenji
AU - Beck, Lucinda
AU - Sharma, Bhavya
AU - Zubeldia, Jose
AU - Baird, Stephen
AU - Tuck, Stephan
AU - Libet, Lev
AU - Spiegelberg, Hans L.
AU - Liu, Fu-Tong
AU - Raz, Eyal
PY - 2002/9
Y1 - 2002/9
N2 - Background: Immunotherapy has gradually fallen out of favor for the treatment of many allergic diseases because of the overall convenience, safety, and efficacy of medications. However, investigations suggest that allergen/immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) conjugates (AICs) might have improved safety and efficacy compared with allergen extracts. Objective: We determined whether changes in the ISS-ODN conjugation ratio would effect the immunogenicity and allergenicity of AIC. Methods: Immunogenicity was determined by means of AIC vaccination of mice, followed by analysis of antigen-specific antibody and cytokine responses. The allergenicity of AIC was determined in mast cell release studies and in murine models of anaphylaxis and the Arthus reaction. Results: AIC induced a stronger immune response than allergen alone or allergen mixed with ISS-ODN, but higher-level ISS-ODN conjugation reduced its immunogenicity modestly. In mast cell degranulation studies AIC was approximately 100-fold less allergenic than native allergen, with stepwise increases in the ODN conjugation ratio leading to stepwise decreases in allergenicity. In anaphylaxis studies death rates were reduced from 100% with native allergen challenge to as low as 0% with high-ratio ISS-ODN AIC challenge. Similar results were obtained in an Arthus reaction model. Conclusion: These investigations establish that AIC is both significantly more immunogenic and less allergenic than native allergens and the techniques used might have further utility for the standardization and optimization of AIC formulations for use in allergic patients.
AB - Background: Immunotherapy has gradually fallen out of favor for the treatment of many allergic diseases because of the overall convenience, safety, and efficacy of medications. However, investigations suggest that allergen/immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) conjugates (AICs) might have improved safety and efficacy compared with allergen extracts. Objective: We determined whether changes in the ISS-ODN conjugation ratio would effect the immunogenicity and allergenicity of AIC. Methods: Immunogenicity was determined by means of AIC vaccination of mice, followed by analysis of antigen-specific antibody and cytokine responses. The allergenicity of AIC was determined in mast cell release studies and in murine models of anaphylaxis and the Arthus reaction. Results: AIC induced a stronger immune response than allergen alone or allergen mixed with ISS-ODN, but higher-level ISS-ODN conjugation reduced its immunogenicity modestly. In mast cell degranulation studies AIC was approximately 100-fold less allergenic than native allergen, with stepwise increases in the ODN conjugation ratio leading to stepwise decreases in allergenicity. In anaphylaxis studies death rates were reduced from 100% with native allergen challenge to as low as 0% with high-ratio ISS-ODN AIC challenge. Similar results were obtained in an Arthus reaction model. Conclusion: These investigations establish that AIC is both significantly more immunogenic and less allergenic than native allergens and the techniques used might have further utility for the standardization and optimization of AIC formulations for use in allergic patients.
KW - Anaphylaxis
KW - CpG motif immunotherapy
KW - Immunostimulatory DNA
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UR - http://www.scopus.com/inward/citedby.url?scp=0036738405&partnerID=8YFLogxK
U2 - 10.1067/mai.2002.126660
DO - 10.1067/mai.2002.126660
M3 - Article
C2 - 12209088
AN - SCOPUS:0036738405
VL - 110
SP - 413
EP - 420
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -