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用重组抗原混合物和副结核分枝杆菌多聚蛋白免疫山羊模型后免疫反应及保护效力的评估

Evaluation of immune responses and protective efficacy in a goat model following immunization with a coctail of recombinant antigens and a polyprotein of Mycobacterium avium subsp. paratuberculosis.

作者信息

Kathaperumal Kumanan, Kumanan Vijayarani, McDonough Sean, Chen Li-Hsuen, Park Sung-Un, Moreira Maria A S, Akey Bruce, Huntley John, Chang Chao-Fu, Chang Yung-Fu

机构信息

Animal Health Diagnostic Center, Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, UpTwoer Road, Ithaca, NY 14853, USA.

出版信息

Vaccine. 2009 Jan 1;27(1):123-35. doi: 10.1016/j.vaccine.2008.10.019. Epub 2008 Oct 26.

DOI:10.1016/j.vaccine.2008.10.019
PMID:18955101
Abstract

The protective efficacy of four recombinant antigens (85A, 85B, superoxide dismutase [SOD], and a fusion polypeptide [Map74F]) of Mycobacterium avium subsp. paratuberculosis (MAP) along with the adjuvant dimethydioctadecyl ammonium bromide (DDA) was assessed in a goat challenge model. Animals were immunized with the four antigens with adjuvant DDA (Group I, eight goat kids) or without the adjuvant (Group II, eight goat kids) or adjuvant only (Group III, nine goat kids). Animals were boostered 3 weeks after the primary vaccination and challenged 3 weeks after the booster. Significant antigen-specific lymphoproliferation was observed in the immunized animals 3 weeks after the booster immunization. This response increased further at 4 weeks after the booster. Similarly, antigen-specific IFN-gamma responses increased in the immunized animals 3 weeks after the booster. The response was significantly higher for 85A and Map74F at 10 weeks after primary vaccination (APV) in Group I animals compared to the other two groups. CD4+ T-cell populations were higher in the vaccinated animals from 6 to 10 weeks APV than those of the control animals. A significant increase in recombinant antigen-specific IFN-gamma gene expression was detected in the vaccinated animals. At necropsy (38 weeks APV), our multicomponent subunit vaccine imparted a significant protection in terms of reduction of MAP burden in target organs as compared to sham-immunized goats. This study indicates that our multicomponent subunit vaccine induced a good Th1 response and conferred protection against MAP infection in a goat challenge model.

摘要

在山羊攻毒模型中评估了副结核分枝杆菌(MAP)的四种重组抗原(85A、85B、超氧化物歧化酶[SOD]和融合多肽[Map74F])与佐剂二甲基二十八烷基溴化铵(DDA)的保护效力。用四种抗原加佐剂DDA免疫动物(第一组,八只山羊羔)或不加佐剂(第二组,八只山羊羔)或仅用佐剂免疫(第三组,九只山羊羔)。初次接种疫苗3周后对动物进行加强免疫,加强免疫3周后进行攻毒。加强免疫3周后,在免疫动物中观察到显著的抗原特异性淋巴细胞增殖。加强免疫4周后,这种反应进一步增强。同样,加强免疫3周后,免疫动物中抗原特异性γ干扰素反应增强。与其他两组相比,第一组动物在初次接种疫苗(APV)10周后,85A和Map74F的反应显著更高。在APV 6至10周期间,接种疫苗的动物体内CD4 + T细胞群体高于对照动物。在接种疫苗的动物中检测到重组抗原特异性γ干扰素基因表达显著增加。尸检时(APV 38周),与假免疫山羊相比,我们的多组分亚单位疫苗在降低靶器官中MAP负荷方面提供了显著保护。这项研究表明,我们的多组分亚单位疫苗在山羊攻毒模型中诱导了良好的Th1反应,并赋予了抗MAP感染的保护作用。

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