The applicant, Dr. Anthony Horner, is an assistant clinical professor of pediatrics at the University of California at San Diego. Dr. Horner trained in allergy and immunology at Boston Children's Hospital from 1991 - 1994, where he studied the CD40 ligand (CD40L) under Dr. Raif Geha. He came to UCSD in 1994 and until recently continued to work on CD40L. Drs. Eyal Raz and Dennis Carson are serving as mentors for the applicant. Dr. Kim Barrett will serve as a consultant/collaborator. The applicant's goals for this project are (1) to acquire further laboratory skills in the area of molecular biology and the use of animal models of allergic disease, (2) to further develop his intellectual skills as a physician scientist, and (3) to create a center of excellence for the diagnosis and management of food allergies at UCSD. The applicant proposes to explore the potential of plasmid DNA (pDNA) immunization to inhibit and reverse Th2-mediated allergic hypersensitivity to orally administered antigen. He will use an established mouse model of oral allergy and anaphylaxis to characterize protection against a Th2-mediated response by (1) intra-dermal allergen gene vaccination using pDNA encoding both allergen and immunostimulatory (IS) sequences and (2) intra-dermal co-injection of native protein plus single domain IS sequence-enriched pDNA. The applicant will then characterize the cellular components of the immune response to vaccination which are required for the development and maintenance of Th1-mediated immunity and the exclusion of Th2-mediated allergic hypersensitivity.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Investigator Award (CIA) (K08)
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Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Takabayashi, Kenji; Libet, Lev; Chisholm, Dugald et al. (2003) Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice. J Immunol 170:3898-905
Horner, Anthony A; Takabayashi, Kenji; Beck, Lucinda et al. (2002) Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity. J Allergy Clin Immunol 110:413-20
Horner, Anthony Adam; Raz, Eyal (2002) Immunostimulatory sequence oligodeoxynucleotide-based vaccination and immunomodulation: two unique but complementary strategies for the treatment of allergic diseases. J Allergy Clin Immunol 110:706-12
Uchijima, M; Raz, E; Carson, D A et al. (2001) Identification of immunostimulatory DNA-induced genes by suppression subtractive hybridization. Biochem Biophys Res Commun 286:688-91
Horner, A A; Datta, S K; Takabayashi, K et al. (2001) Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites. J Immunol 167:1584-91
Horner, A A; Van Uden, J H; Zubeldia, J M et al. (2001) DNA-based immunotherapeutics for the treatment of allergic disease. Immunol Rev 179:102-18
Nguyen, M D; Cinman, N; Yen, J et al. (2001) DNA-based vaccination for the treatment of food allergy. Allergy 56 Suppl 67:127-30
Horner, A A; Widhopf, G F; Burger, J A et al. (2001) Immunostimulatory DNA inhibits IL-4-dependent IgE synthesis by human B cells. J Allergy Clin Immunol 108:417-23
Horner, A A; Nguyen, M D; Ronaghy, A et al. (2000) DNA-based vaccination reduces the risk of lethal anaphylactic hypersensitivity in mice. J Allergy Clin Immunol 106:349-56
Horner, A A; Raz, E (2000) Immunostimulatory-sequence DNA is an effective mucosal adjuvant. Curr Top Microbiol Immunol 247:185-98

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