Department of R&D, Immunomic Therapeutics, Inc. (ITI), Rockville, MD 20850, USA.
J Immunol Res. 2016;2016:4857869. doi: 10.1155/2016/4857869. Epub 2016 Apr 30.
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.
由日本扁柏(JRC)花粉引起的过敏影响了多达三分之一的日本人,因此需要开发一种有效的治疗方法。我们利用溶酶体相关膜蛋白-1(LAMP-1)的溶酶体靶向特性,制造了编码 LAMP-1 以及 JRC 花粉中免疫优势过敏原 CryJ1 或 CryJ2 序列的 DNA 疫苗。这种新策略旨在使针对目标过敏原的 CD4 T 细胞反应偏向于非过敏的 Th1 反应。将 CryJ1-LAMP 和 CryJ2-LAMP 给予 BALB/c 小鼠,并进行纵向检测抗原特异性 Th1 型 IgG2a 和 Th2 型 IgG1 抗体以及 IgE 抗体。我们还从免疫小鼠中分离出不同的 T 细胞群,并将其过继转移到 naive 小鼠中,然后进行 CryJ1/CryJ2 蛋白加强。我们证明 CryJ-LAMP 免疫的小鼠产生高水平的 IFN-γ 和抗 CryJ1 或抗 CryJ2 IgG2a 抗体,以及低水平的 IgE 抗体,表明诱导了 Th1 反应。此外,我们发现 CD4(+) T 细胞是该过敏模型中 DNA 疫苗接种的免疫效应物。总之,我们的结果表明,CryJ-LAMP 疫苗通过偏向 Th1/Th2 反应,有可能成为治疗 JRC 诱导过敏的有效方法。