Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Nanjing 210009, China.
Vaccine. 2011 Feb 4;29(7):1455-62. doi: 10.1016/j.vaccine.2010.12.031. Epub 2010 Dec 24.
Herpes stromal keratitis (HSK) is a chronic inflammatory process caused by the infection of herpes simplex virus type 1 (HSV-1). Development of a HSV-1 vaccine is a priority because these infections are common and cannot be well prevented. It appears that the potential of nanocarriers in DNA vaccination will be required to augment the immune response to DNA vaccines. Therefore, in the study, nanoparticles Fe(3)O(4) coated with glutamic acid, DNA vaccine pRSC-gD-IL-21 and polyethylenimine were prepared and immunized in the mice by ocular mucosal administration. The immune responses and protection efficiency against HSV-1 challenge were also tested. The results showed that the nanoparticles containing DNA vaccine pRSC-gD-IL-21 induced mice to generate higher levels of specific neutralizing antibody, sIgA in tears, and IFN-γ, IL-4 in serum, and to enhance the cytotoxicities of NK cells and splenocytes as well as splenocyte proliferative response to glycoprotein D compared with those of the control mice. More importantly, the mice immunized with the experimental vaccine showed less HSK degree than that of the control mice after HSV-1 challenge of the murine ocular mucosa. In conclusion, an ocular mucosal administration of nanoparticles containing DNA vaccine confers strong specific immune responses and effective inhibition of HSK in a HSV-1 infected murine model.
单纯疱疹性基质角膜炎(HSK)是由单纯疱疹病毒 1 型(HSV-1)感染引起的慢性炎症过程。开发 HSV-1 疫苗是当务之急,因为这些感染很常见,而且无法很好地预防。似乎需要纳米载体来增强 DNA 疫苗的免疫反应,以增强对 DNA 疫苗的免疫反应。因此,在这项研究中,通过眼部黏膜给药,制备了用谷氨酸包被的纳米粒子 Fe(3)O(4)、DNA 疫苗 pRSC-gD-IL-21 和聚乙烯亚胺,并在小鼠中进行了免疫接种。还测试了针对 HSV-1 攻击的免疫反应和保护效率。结果表明,含有 DNA 疫苗 pRSC-gD-IL-21 的纳米粒子诱导小鼠产生更高水平的特异性中和抗体、泪液中的 sIgA 以及血清中的 IFN-γ、IL-4,并增强 NK 细胞和脾细胞的细胞毒性以及脾细胞对糖蛋白 D 的增殖反应,与对照组小鼠相比。更重要的是,与对照组小鼠相比,在 HSV-1 攻击小鼠眼黏膜后,用实验疫苗免疫的小鼠 HSK 程度较低。总之,眼部黏膜给予含有 DNA 疫苗的纳米粒子可在 HSV-1 感染的小鼠模型中引起强烈的特异性免疫反应并有效抑制 HSK。