PRRSV流行毒株NSP2遗传变异分析及其活疫苗的安全性评价
摘要
猪繁殖与呼吸综合征猪繁殖与呼吸综合征(Porcine Reproductive and RespiratorySyndrome, PRRS)是由PRRS病毒(PRRS Vrius, PRRSV)引起一种以母猪繁殖障碍和仔猪呼吸道症状为主要特征的传染病，该病是目前造成世界养猪业经济损失最为严重的传染病之一。根据蓝耳病病毒基因组的分子特征和致病性可将其分为经典PRRSV毒株和高致病性PRRSV毒株。高致病性PRRSV毒株2007年在我国南方流行蔓延，也是导致“猪高热病”的主要病原之一。高致病性PRRSV毒株以NSP2缺失1+29aa作为其重要的分子特征区分于经典PRRSV毒株。本研究对不同地区和时间发病猪的病料进行了PRRSV分离与鉴定，并分析了PRRSV分离毒株NSP2遗传衍化规律。针对目前应用PRRS活疫苗进行了安全性评价，对PRRS活疫苗的应用效果进行了调查。
收集2005～2010年来自我国12省份的1300份疑似PRRSV感染发病猪的病料，通过肺泡巨噬细胞和Marc-145细胞进行病毒分离，并通过IFA和RT-PCR对分离毒株进行鉴定，通过电子显微镜可以观察到45～65nm的病毒粒子，分离得到39株PRRSV。对所有的分离毒株序列测定后发现，35株PRRSV的NSP2上有1aa+29aa等2处缺失（H型）；3株PRRSV的NSP2上具有1aa+4aa+29aa等3处缺失（Z型）；1株PRRSV的NSP2上具有1aa的缺失（G型）。连同他人分离的3株PRRSV的NSP2具有2处大片段缺失（29aa+30aa的缺失）的W型共有4个NSP2的氨基酸缺失型。根据NSP2变异规律，包括以CH-1a株为代表C型在内，可以将PRRSV分离毒株分成5个型（C、G、H、Z和W型）。
对目前商品化的经典和高致病性PRRS活疫苗进行了安全评价，将2类PRRS活疫苗按单剂量重复接种和大剂量分别接种保育猪和怀孕后期的母猪，试验结果表明经典PRRS活疫苗对母猪和仔猪是安全的，经典PRRS活疫苗免疫猪的毒血症和散毒时间较短，并且免疫母猪产下的仔猪的无带毒现象。而高致病性PRRS活疫苗免疫猪的毒血症持续时间可达4周以上，并导致所有免疫的怀孕母猪发生繁殖障碍，并导致其所产的仔猪仍有大部分仔猪带毒。
对PRRS活疫苗的应用效果进行了跟踪调查，共调查355个猪场，其中母猪使用经典PRRS活疫苗占使用PRRS疫苗猪场的61.28%；使用高致病性PRRS活疫苗免疫母猪的猪场占使用PRRS疫苗猪场的13.70%。仔猪使用PRRS活疫苗占使用PRRS疫苗猪场的75.00%；仔猪使用高致病性PRRS活疫苗占使用PRRS疫苗猪场的15.58%。对经典PRRS活疫苗的免疫认可度为79.60%以上；而对高致病性PRRS活疫苗的免疫认可度为低于63.50%。对经典PRRS活疫苗的安全认可度为79.95%以上；而对高致病性PRRS活疫苗的安全认可度为低于67.31%，调查结果表明经典PRRS活疫苗是目前应用最广和最为信赖的PRRS疫苗。
Porcine reproductive and respiratory syndrome (PRRS) is a most important infectious diseasecaused by PRRS virus (PRRSV)，which has been characterized by reproductive failure during lateterm gestation in sows and respiratory tract distress in piglets. It can cause enormous economiclosses in the swine industry all over the world. The PRRSV was divided into classic PRRSV andhighly pathogenic PRRSV (HP-PRRSV) based on its pathogenicity and genomic molecularcharacteristics. The HP-PRRSV had been epidemic in South of China in2007, and the1+29amino acid (aa) deletion in nonstructural protein2(NSP2) is the important molecular features ofHP-PRRSV that distinguish from the classic PRRSV strain. To clarify epidemic strains origin andvariation characteristics, and the safety of the PRRS live vaccine, the PRRSV strains were isolatedfrom the swine suspected PRRSV infection in different time and regions, and NSP2geneticevolution characteristics of PRRSV isolates was analyzed. PRRS live vaccine safety wasevaluated, and the PRRS live vaccine application effect was investigated in this study.
1300samples were collected from pigs suspected PRRSV infection in12provinces in2005～2010, the PRRSV were isolated by alveolar macrophages and Marc-145cells. The isolatesstrain were identified by RT-PCR and IFA, and virion with the diameter of about45-65nm wasshowed by electronic microscopy. Eventually,39strains of PRRSV were isolated in this research.After the Nsp2genes of the isolates were cloned and analyzed, we found that35isolates contained1aa+29aa deletion in NSP2(type H), and3isolates contained1aa+4aa+29aa deletion in NSP2(type Z), and1strains contained1aa deletion in NSP2(type G). There are3types of NSP2deletion virus, and others3isolates contained30aa+29aa deletion in NSP2(type W). Accordingto the NSP2variation, including CH-1a as representatives of type C, the PRRSV strains can bedivided into5type isolates (C, G, H, Z and W type).
The safety of the commercial classic and highly pathogenic PRRS live vaccine was evaluatedby the animal experiment. Two PRRS live vaccine were inoculated nursery pig and late pregnantsows by single repeated dose or high dose test. The results showed that the classical PRRS vaccineon sows and piglets is safe, the pigs inoculated with classic PRRS live vaccine have shorterviremia and shedding time, and the piglets from vaccinated sows were not infected by classicPRRSV strain. While the pigs inoculated with highly pathogenic PRRS vaccine have a longviremia and shedding time (more than4weeks), highly pathogenic PRRS vaccine can result invaccinated pregnant sows reproductive failure, and the most piglets from vaccinated sows wereinfected by highly pathogenic PRRSV strain.
A total of355farms were investigated about the application effect of PRRS live vaccine. Forsows,61.28%of them use classical PRRS live vaccine; however, only13.7%of them use highlypathogenic PRRS live vaccine. For piglets,75.00%of them use classical PRRS live vaccine, and 15.58%of them use highly pathogenic PRRS live vaccine. Satisfaction survey results showed thatmore than79.6%of swine farms are satisfied with the use of classical PRRS live vaccine, however,less than63.3%of swine farms are satisfied with the use of highly pathogenic PRRS live vaccine.More than79.95%of swine farms approved the safety of classic PRRS live vaccine, but less than67.31%of swine farms approved the safety of the highly pathogenic PRRS live vaccine. Thesurvey results demonstrated that classic PRRS live vaccine is currently the most widely used andmost trusted PRRS vaccine for users.
收集2005～2010年来自我国12省份的1300份疑似PRRSV感染发病猪的病料，通过肺泡巨噬细胞和Marc-145细胞进行病毒分离，并通过IFA和RT-PCR对分离毒株进行鉴定，通过电子显微镜可以观察到45～65nm的病毒粒子，分离得到39株PRRSV。对所有的分离毒株序列测定后发现，35株PRRSV的NSP2上有1aa+29aa等2处缺失（H型）；3株PRRSV的NSP2上具有1aa+4aa+29aa等3处缺失（Z型）；1株PRRSV的NSP2上具有1aa的缺失（G型）。连同他人分离的3株PRRSV的NSP2具有2处大片段缺失（29aa+30aa的缺失）的W型共有4个NSP2的氨基酸缺失型。根据NSP2变异规律，包括以CH-1a株为代表C型在内，可以将PRRSV分离毒株分成5个型（C、G、H、Z和W型）。
对目前商品化的经典和高致病性PRRS活疫苗进行了安全评价，将2类PRRS活疫苗按单剂量重复接种和大剂量分别接种保育猪和怀孕后期的母猪，试验结果表明经典PRRS活疫苗对母猪和仔猪是安全的，经典PRRS活疫苗免疫猪的毒血症和散毒时间较短，并且免疫母猪产下的仔猪的无带毒现象。而高致病性PRRS活疫苗免疫猪的毒血症持续时间可达4周以上，并导致所有免疫的怀孕母猪发生繁殖障碍，并导致其所产的仔猪仍有大部分仔猪带毒。
对PRRS活疫苗的应用效果进行了跟踪调查，共调查355个猪场，其中母猪使用经典PRRS活疫苗占使用PRRS疫苗猪场的61.28%；使用高致病性PRRS活疫苗免疫母猪的猪场占使用PRRS疫苗猪场的13.70%。仔猪使用PRRS活疫苗占使用PRRS疫苗猪场的75.00%；仔猪使用高致病性PRRS活疫苗占使用PRRS疫苗猪场的15.58%。对经典PRRS活疫苗的免疫认可度为79.60%以上；而对高致病性PRRS活疫苗的免疫认可度为低于63.50%。对经典PRRS活疫苗的安全认可度为79.95%以上；而对高致病性PRRS活疫苗的安全认可度为低于67.31%，调查结果表明经典PRRS活疫苗是目前应用最广和最为信赖的PRRS疫苗。
Porcine reproductive and respiratory syndrome (PRRS) is a most important infectious diseasecaused by PRRS virus (PRRSV)，which has been characterized by reproductive failure during lateterm gestation in sows and respiratory tract distress in piglets. It can cause enormous economiclosses in the swine industry all over the world. The PRRSV was divided into classic PRRSV andhighly pathogenic PRRSV (HP-PRRSV) based on its pathogenicity and genomic molecularcharacteristics. The HP-PRRSV had been epidemic in South of China in2007, and the1+29amino acid (aa) deletion in nonstructural protein2(NSP2) is the important molecular features ofHP-PRRSV that distinguish from the classic PRRSV strain. To clarify epidemic strains origin andvariation characteristics, and the safety of the PRRS live vaccine, the PRRSV strains were isolatedfrom the swine suspected PRRSV infection in different time and regions, and NSP2geneticevolution characteristics of PRRSV isolates was analyzed. PRRS live vaccine safety wasevaluated, and the PRRS live vaccine application effect was investigated in this study.
1300samples were collected from pigs suspected PRRSV infection in12provinces in2005～2010, the PRRSV were isolated by alveolar macrophages and Marc-145cells. The isolatesstrain were identified by RT-PCR and IFA, and virion with the diameter of about45-65nm wasshowed by electronic microscopy. Eventually,39strains of PRRSV were isolated in this research.After the Nsp2genes of the isolates were cloned and analyzed, we found that35isolates contained1aa+29aa deletion in NSP2(type H), and3isolates contained1aa+4aa+29aa deletion in NSP2(type Z), and1strains contained1aa deletion in NSP2(type G). There are3types of NSP2deletion virus, and others3isolates contained30aa+29aa deletion in NSP2(type W). Accordingto the NSP2variation, including CH-1a as representatives of type C, the PRRSV strains can bedivided into5type isolates (C, G, H, Z and W type).
The safety of the commercial classic and highly pathogenic PRRS live vaccine was evaluatedby the animal experiment. Two PRRS live vaccine were inoculated nursery pig and late pregnantsows by single repeated dose or high dose test. The results showed that the classical PRRS vaccineon sows and piglets is safe, the pigs inoculated with classic PRRS live vaccine have shorterviremia and shedding time, and the piglets from vaccinated sows were not infected by classicPRRSV strain. While the pigs inoculated with highly pathogenic PRRS vaccine have a longviremia and shedding time (more than4weeks), highly pathogenic PRRS vaccine can result invaccinated pregnant sows reproductive failure, and the most piglets from vaccinated sows wereinfected by highly pathogenic PRRSV strain.
A total of355farms were investigated about the application effect of PRRS live vaccine. Forsows,61.28%of them use classical PRRS live vaccine; however, only13.7%of them use highlypathogenic PRRS live vaccine. For piglets,75.00%of them use classical PRRS live vaccine, and 15.58%of them use highly pathogenic PRRS live vaccine. Satisfaction survey results showed thatmore than79.6%of swine farms are satisfied with the use of classical PRRS live vaccine, however,less than63.3%of swine farms are satisfied with the use of highly pathogenic PRRS live vaccine.More than79.95%of swine farms approved the safety of classic PRRS live vaccine, but less than67.31%of swine farms approved the safety of the highly pathogenic PRRS live vaccine. Thesurvey results demonstrated that classic PRRS live vaccine is currently the most widely used andmost trusted PRRS vaccine for users.
引文
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