Ou Jing, Shi Wendan, Xu Yu, Tao Zezhang
Department of Otorhinolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Otorhinolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Ann Allergy Asthma Immunol. 2014 Dec;113(6):658-665.e1. doi: 10.1016/j.anai.2014.08.015. Epub 2014 Sep 17.
The worldwide prevalence of allergic rhinitis (AR) is increasing, whereas treatments for AR remain limited in effect. Therefore, a new type of effective drug is eagerly in demand.
To create a hypoallergenic vaccine by forced ubiquitination.
In the present study, we constructed a DNA vaccine coexpressing Der p 1 allergen and murine ubiquitin, which used chitosan as a carrier. Through the vitro and vivo experiments, we evaluated its protective efficacy against AR.
The results indicated that the DNA vaccine pVAX1-Ub-Derp1/CS had been successfully constructed. This nanoparticle could not only transfect 293T cells in vitro but also transform cells in vivo. The inflammation of nasal mucosa in an AR murine model via immunization with pVAX1-Ub-Derp1/CS was less severe than those without treatments. Furthermore, it found that mice immunized with pVAX1-Ub-Derp1/CS generated a high level of specific IgG but a low level of specific IgE (P < .01). The significantly increased levels of interferon-γ and the significantly decreased levels of interleukins 4, 10, and 17 indicated that a TH1-type response was elicited by immunization with pVAX1-Ub-Derp1/CS (P < .01). This effect was especially stronger through intranasal immunization.
Nasal mucosal immunization and ubiquitination are efficacious strategies to enhance the efficiency and safety of DNA vaccine. The nanoparticle pVAX1-Ub-Derp1/CS is expected to be a new kind of effective vaccine for AR.
全球变应性鼻炎(AR)的患病率正在上升,而AR的治疗效果仍然有限。因此,迫切需要一种新型的有效药物。
通过强制泛素化制备一种低变应原性疫苗。
在本研究中,我们构建了一种共表达Der p 1变应原和小鼠泛素的DNA疫苗,该疫苗以壳聚糖作为载体。通过体外和体内实验,我们评估了其对AR的保护效果。
结果表明,DNA疫苗pVAX1-Ub-Derp1/CS已成功构建。这种纳米颗粒不仅能在体外转染293T细胞,还能在体内转化细胞。用pVAX1-Ub-Derp1/CS免疫AR小鼠模型,其鼻黏膜炎症比未治疗的小鼠轻。此外,发现用pVAX1-Ub-Derp1/CS免疫的小鼠产生高水平的特异性IgG但低水平的特异性IgE(P <.01)。干扰素-γ水平显著升高,白细胞介素4、10和17水平显著降低,表明用pVAX1-Ub-Derp1/CS免疫引发了TH1型反应(P <.01)。通过鼻内免疫,这种效果尤其明显。
鼻黏膜免疫和泛素化是提高DNA疫苗效率和安全性的有效策略。纳米颗粒pVAX1-Ub-Derp1/CS有望成为一种新型的有效AR疫苗。