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表达弓形虫 SAG1 和 MIC3 蛋白的两种重组伪狂犬病病毒的免疫原性和保护效力。

Immunogenicity and protective efficacy of two recombinant pseudorabies viruses expressing Toxoplasma gondii SAG1 and MIC3 proteins.

机构信息

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Sizhishan Street, Hubei, Wuhan 430070, PR China.

出版信息

Vet Parasitol. 2011 Sep 27;181(2-4):215-21. doi: 10.1016/j.vetpar.2011.04.039. Epub 2011 May 5.

DOI:10.1016/j.vetpar.2011.04.039
PMID:21632181
Abstract

Toxoplasma gondii is one of the most common parasitic pathogens in humans and warm-blooded animals, causing toxoplasmosis. One of the efficient ways to control this disease is immunization. In this study, two recombinant pseudorabies virus (PRV) expressing TgSAG1 (rPRV-SAG1) and TgMIC3 (rPRV-MIC3) based on the PRV vaccine strain were developed by homologous recombination and used for immunizing BALB/c mice. Ninety BALB/c mice were randomly divided into five groups including four experimental groups (inoculated twice in 4 weeks interval with PRV TK-/gG-/EGFP+, rPRV-SAG1, rPRV-MIC3, rPRV-SAG1+rPRV-MIC3, respectively) and one control group (inoculated with medium). All mice vaccinated with rPRV developed a high level of specific antibody responses against T. gondii lysate antigen (TLA), a strong increase of the splenocyte proliferative response, and significant levels of IFN-γ and IL-2 production. These results demonstrated that rPRV could induce significant humoral and cellular Th1 immune responses. Moreover, rPRV immunization induced partial protection against a lethal challenge with T. gondii RH strain, and neutralizing antibodies against PRV in a BALB/c mouse model. The mice immunized with the rPRV-SAG1 and rPRV-MIC3 cocktail could develop higher T. gondii-specific IgG antibodies and lymphocyte proliferative responses and conferred more efficient protection against T. gondii challenge. These results suggested that expression of protective antigens of T. gondii in PRV is a novel approach towards the development of a vaccine against both animal pseudorabies and toxoplasmosis.

摘要

刚地弓形虫是人类和温血动物中最常见的寄生虫病原体之一,可引起弓形体病。控制这种疾病的有效方法之一是免疫接种。在这项研究中,通过同源重组开发了两种基于 PRV 疫苗株表达 TgSAG1(rPRV-SAG1)和 TgMIC3(rPRV-MIC3)的重组伪狂犬病病毒(PRV)(rPRV-SAG1 和 rPRV-MIC3),并用于免疫 BALB/c 小鼠。90 只 BALB/c 小鼠随机分为五组,包括四个实验组(分别用 PRV TK-/gG-/EGFP+、rPRV-SAG1、rPRV-MIC3、rPRV-SAG1+rPRV-MIC3 接种两次,间隔 4 周)和一个对照组(接种培养基)。用 rPRV 接种的所有小鼠均对弓形虫裂解抗原(TLA)产生高水平的特异性抗体反应,脾细胞增殖反应明显增强,IFN-γ 和 IL-2 产生水平显著升高。这些结果表明,rPRV 可诱导显著的体液和细胞 Th1 免疫反应。此外,rPRV 免疫接种可部分保护 RH 株弓形虫致死性攻击,并中和 BALB/c 小鼠模型中的 PRV 中和抗体。rPRV-SAG1 和 rPRV-MIC3 鸡尾酒免疫的小鼠可产生更高的弓形虫特异性 IgG 抗体和淋巴细胞增殖反应,并对弓形虫攻击提供更有效的保护。这些结果表明,弓形虫保护性抗原在 PRV 中的表达是开发针对动物伪狂犬病和弓形体病的新型疫苗的一种新方法。

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