CryJ-LAMP DNA Vaccines for Japanese Red Cedar Allergy Induce Robust Th1-Type Immune Responses in Murine Model

• Published in: Journal of immunology research 2016-01, Vol.2016 (2016), p.1-15
• Main Authors: Heiland, Teri, Marketon, Anthony, Connolly, Michael, Su, Yan
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Allergens - chemistry; Allergens - genetics; Allergens - immunology; Animals; CD4-Positive T-Lymphocytes - immunology; Cryptomeria - immunology; Deoxyribonucleic acid; Disease Models, Animal; DNA; Genes; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunoglobulins; Immunology; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Laboratories; Lysosomal Membrane Proteins - administration & dosage; Lysosomal Membrane Proteins - genetics; Lysosomal Membrane Proteins - immunology; Medical research; Mice; Mice, Inbred BALB C; Plasmids; Proteins; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - therapy; Studies; Th1 Cells - immunology; Th1-Th2 Balance; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Vaccines, DNA - therapeutic use
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2016/4857869

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.