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一种嵌合猪圆环病毒(PCV),其将致病性2型猪圆环病毒(PCV2)的免疫原性衣壳基因克隆到非致病性PCV1的基因组主干中,可诱导猪对PCV2感染产生保护性免疫。

A chimeric porcine circovirus (PCV) with the immunogenic capsid gene of the pathogenic PCV type 2 (PCV2) cloned into the genomic backbone of the nonpathogenic PCV1 induces protective immunity against PCV2 infection in pigs.

作者信息

Fenaux M, Opriessnig T, Halbur P G, Elvinger F, Meng X J

机构信息

Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0342, USA.

出版信息

J Virol. 2004 Jun;78(12):6297-303. doi: 10.1128/JVI.78.12.6297-6303.2004.

Abstract

Porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic wasting syndrome in pigs, whereas PCV1 is nonpathogenic. We previously demonstrated that a chimeric PCV1-2 virus (with the immunogenic capsid gene of PCV2 cloned into the backbone of PCV1) induces an antibody response to the PCV2 capsid protein and is attenuated in pigs. Here, we report that the attenuated chimeric PCV1-2 induces protective immunity to wild-type PCV2 challenge in pigs. A total of 48 specific-pathogen-free piglets were randomly and equally assigned to four groups of 12 pigs each. Pigs in group 1 were vaccinated by intramuscular injection with 200 microg of the chimeric PCV1-2 infectious DNA clone. Pigs in group 2 were vaccinated by intralymphoid injection with 200 microg of a chimeric PCV1-2 infectious DNA clone. Pigs in group 3 were vaccinated by intramuscular injection with 10(3.5) 50% tissue culture infective doses (TCID(50)) of the chimeric PCV1-2 live virus. Pigs in group 4 were not vaccinated and served as controls. By 42 days postvaccination (DPV), the majority of pigs had seroconverted to PCV2 capsid antibody. At 42 DPV, all pigs were challenged intranasally and intramuscularly with 2 x 10(4.5) TCID(50) of a wild-type pathogenic PCV2 virus. By 21 days postchallenge (DPC), 9 out of the 12 group 4 pigs were viremic for PCV2. Vaccinated animals in groups 1 to 3 had no detectable PCV2 viremia after challenge. At 21 DPC the lymph nodes in the nonvaccinated pigs were larger (P < 0.05) than those of vaccinated pigs. The PCV2 genomic copy loads in lymph nodes were reduced (P < 0.0001) in vaccinated pigs. Moderate amounts of PCV2 antigen were detected in most lymphoid tissues of nonvaccinated pigs but in only 1 of 36 vaccinated pigs. Mild-to-severe lymphoid depletion and histiocytic replacement were detected in lymphoid tissues in the majority of nonvaccinated group 4 pigs but in only a few vaccinated group 1 to 3 pigs. The data from this study indicated that when given intramuscularly in pigs, the attenuated chimeric PCV1-2 live virus, as well as the chimeric PCV1-2 infectious DNA clone, induces protective immunity against PCV2 infection and could potentially serve as an effective vaccine.

摘要

猪圆环病毒2型(PCV2)与猪断奶后多系统消耗综合征有关,而PCV1无致病性。我们之前证明,一种嵌合PCV1-2病毒(将PCV2的免疫原性衣壳基因克隆到PCV1的骨架中)可诱导针对PCV2衣壳蛋白的抗体反应,并且在猪体内减毒。在此,我们报告减毒嵌合PCV1-2可诱导猪对野生型PCV2攻击产生保护性免疫。总共48头无特定病原体仔猪被随机且平均分为四组,每组12头猪。第1组猪通过肌肉注射接种200微克嵌合PCV1-2感染性DNA克隆。第2组猪通过淋巴内注射接种200微克嵌合PCV1-2感染性DNA克隆。第3组猪通过肌肉注射接种10(3.5) 50%组织培养感染剂量(TCID(50))的嵌合PCV1-2活病毒。第4组猪不接种,作为对照。到接种后42天(DPV),大多数猪血清转化为PCV2衣壳抗体。在42 DPV时,所有猪通过鼻内和肌肉内接种2×10(4.5) TCID(50)的野生型致病性PCV2病毒进行攻击。到攻击后21天(DPC),第4组的12头猪中有9头出现PCV2病毒血症。第1至3组接种疫苗的动物在攻击后未检测到PCV2病毒血症。在21 DPC时,未接种疫苗的猪的淋巴结比接种疫苗的猪的淋巴结大(P < 0.05)。接种疫苗的猪的淋巴结中PCV2基因组拷贝数减少(P < 0.0001)。在未接种疫苗的猪的大多数淋巴组织中检测到中等量的PCV2抗原,但在36头接种疫苗的猪中仅1头检测到。在第4组大多数未接种疫苗的猪的淋巴组织中检测到轻度至重度淋巴细胞耗竭和组织细胞替代,但在第1至3组接种疫苗的猪中仅少数检测到。本研究数据表明,在猪肌肉注射时,减毒嵌合PCV1-2活病毒以及嵌合PCV1-2感染性DNA克隆可诱导针对PCV2感染的保护性免疫,并有可能作为一种有效的疫苗。

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