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一种含LeIF和TSA基因的二价DNA疫苗对小鼠皮肤利什曼病的免疫原性和疗效

Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis.

作者信息

Maspi Nahid, Ghaffarifar Fatemeh, Sharifi Zohreh, Dalimi Abdolhossein, Dayer Mohammad Saaid

机构信息

Department of Medical Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

出版信息

APMIS. 2017 Mar;125(3):249-258. doi: 10.1111/apm.12651.

DOI:10.1111/apm.12651
PMID:28233451
Abstract

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF-TSA fusion against cutaneous leishmaniasis pEGFP-N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3-12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN-γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF-TSA, respectively, than in PBS group at 12th week post infection. IFN/IL-4 and IgG2a/IgG1 ratios indicated that group receiving LeIF-TSA fusion had the highest IFN-γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN-γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis.

摘要

目前尚无用于预防和消除利什曼病的有效疫苗。因此,我们评估了单独含有LeIF、TSA基因的DNA疫苗或LeIF - TSA融合疫苗对皮肤利什曼病的保护作用,以pEGFP - N1质粒(空载体)和磷酸盐缓冲盐水(PBS)作为对照组。因此,在感染硕大利什曼原虫之前和之后评估细胞免疫和体液免疫反应。在攻击后3 - 12周也测量病变直径。与对照组相比,所有用编码利什曼原虫抗原的质粒DNA免疫的小鼠均诱导了以IFN -γ和IgG2a水平升高为特征的部分免疫(p < 0.001)。此外,与空载体组和PBS组的小鼠相比,免疫小鼠的平均病变大小显著减小(p < 0.05)。在感染后第12周,接种LeIF、TSA和LeIF - TSA的组的病变直径分别比PBS组减小了29.3%、34.1%和46.2%。IFN/IL - 4和IgG2a/IgG1比值表明,接受LeIF - TSA融合疫苗的组具有最高的IFN -γ和IgG2a水平。在本研究中,DNA免疫促进了以较高的IFN -γ和IgG2a水平以及病变大小减小为特征的Th1免疫反应。这些结果表明,包含两种不同抗原的二价疫苗可能诱导针对利什曼病更有效的免疫反应。

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