title: CryJ-LAMP DNA Vaccines for Japanese Red Cedar Allergy Induce Robust Th1-Type Immune Responses in Murine Model.
abstract: Allergies caused by Japanese Red Cedar (JRC) pollen affect up to a third of Japanese people, necessitating development of an effective therapeutic. We utilized the lysosomal targeting property of lysosomal-associated membrane protein-1 (LAMP-1) to make DNA vaccines that encode LAMP-1 and the sequences of immunodominant allergen CryJ1 or CryJ2 from the JRC pollen. This novel strategy is designed to skew the CD4 T cell responses to the target allergens towards a nonallergenic Th1 response. CryJ1-LAMP and CryJ2-LAMP were administrated to BALB/c mice and antigen-specific Th1-type IgG2a and Th2-type IgG1 antibodies, as well as IgE antibodies, were assayed longitudinally. We also isolated different T cell populations from immunized mice and adoptively transferred them into naïve mice followed by CryJ1/CryJ2 protein boosts. We demonstrated that CryJ-LAMP immunized mice produce high levels of IFN-γ and anti-CryJ1 or anti-CryJ2 IgG2a antibodies and low levels of IgE antibodies, suggesting that a Th1 response was induced. In addition, we found that CD4(+) T cells are the immunological effectors of DNA vaccination in this allergy model. Together, our results suggest the CryJ-LAMP Vaccine has a potential as an effective therapeutic for JRC induced allergy by skewing Th1/Th2 responses.
authors.affiliation: Department of R&D, Immunomic Therapeutics, Inc. (ITI), Rockville, MD 20850, USA.
authors.forename: Yan
authors.identifier: 0000-0002-7193-472X
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of R&D, Immunomic Therapeutics, Inc. (ITI), Rockville, MD 20850, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Connolly
authors.affiliation: Department of R&D, Immunomic Therapeutics, Inc. (ITI), Rockville, MD 20850, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Marketon
authors.affiliation: Department of R&D, Immunomic Therapeutics, Inc. (ITI), Rockville, MD 20850, USA.
authors.forename: Teri
authors.identifier: 0000-0002-3276-4713
authors.initials: T
authors.lastname: Heiland
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D032485:Cryptomeria / Q000276:immunology*; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051907:Lysosomal Membrane Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000628:therapy; D018417:Th1 Cells / Q000276:immunology*; D058408:Th1-Th2 Balance; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D007371:Interferon-gamma; D051907:Lysosomal Membrane Proteins; D019444:Vaccines, DNA; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1