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      An inactivated gE-deleted pseudorabies vaccine provides complete clinical protection and reduces virus shedding against challenge by a Chinese pseudorabies variant

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          Abstract

          Background

          Since the end of 2011 an outbreak of pseudorabies affected Chinese pig herds that had been vaccinated with the commercial vaccine made of Bartha K61 strain. It is now clear that the outbreak was caused by an emergent PRV variant. Even though vaccines made of PRV Bartha K61 strain can confer certain cross protection against PRV variants based on experimental data, less than optimal clinical protection and virus shedding reduction were observed, making the control or eradication of this disease difficult.

          Results

          An infectious clone of PRV AH02LA strain was constructed to generate a gE deletion mutant PRV(LA-A B) strain. PRV(LA-A B) strain can reach a titer of 10 8.43 TCID 50 /mL (50% tissue culture infectious dose) on BHK-21 cells. To evaluate the efficiency of the inactivated vaccine made of PRV(LA-A B) strain, thirty 3-week-old PRV-negative piglets were divided randomly into six groups for vaccination and challenge test. All five piglets in the challenge control showed typical clinical symptoms of pseudorabies post challenge. Sneezing and nasal discharge were observed in four and three piglets in groups C(vaccinated with inactivated PRV Bartha K61 strain vaccine) and D(vaccinated with live PRV Bartha K61 strain vaccine) respectively. In contrast, piglets in both groups A(vaccinated with inactivated PRV LA-AB strain vaccine) and B(vaccinated with inactivated PRV LA-A B strain vaccine with adjuvant) presented mild or no clinical symptoms. Moreover, viral titers detected via nasal swabs were approximately 100 times lower in group B than in the challenge control, and the duration of virus shedding (3–4 days) was shorter than in either the challenge control (5–10 days) or groups C and D (5–6 days).

          Conclusions

          The infectious clone constructed in this study harbors the whole genome of the PRV variant AH02LA strain. The gE deletion mutant PRV(LA-A B)strain generated from PRV AH02LA strain can reach a high titer on BHK-21 cells. An inactivated vaccine of PRV LA-A B provides clinical protection and significantly reduces virus shedding post challenge, especially if accompanied by the adjuvant CVC1302. While Inactivated or live vaccines made of PRV Barth K61 strain can provide only partial protection in this test.

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          Most cited references25

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          Cloning and stable maintenance of 300-kilobase-pair fragments of human DNA in Escherichia coli using an F-factor-based vector.

          A bacterial cloning system for mapping and analysis of complex genomes has been developed. The BAC system (for bacterial artificial chromosome) is based on Escherichia coli and its single-copy plasmid F factor. It is capable of maintaining human genomic DNA fragments of greater than 300 kilobase pairs. Individual clones of human DNA appear to be maintained with a high degree of structural stability in the host, even after 100 generations of serial growth. Because of high cloning efficiency, easy manipulation of the cloned DNA, and stable maintenance of inserted DNA, the BAC system may facilitate construction of DNA libraries of complex genomes with fuller representation and subsequent rapid analysis of complex genomic structure.
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            Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome.

            A strategy for cloning and mutagenesis of an infectious herpesvirus genome is described. The mouse cytomegalovirus genome was cloned and maintained as a 230 kb bacterial artificial chromosome (BAC) in E. coli. Transfection of the BAC plasmid into eukaryotic cells led to a productive virus infection. The feasibility to introduce targeted mutations into the BAC cloned virus genome was shown by mutation of the immediate-early 1 gene and generation of a mutant virus. Thus, the complete construction of a mutant herpesvirus genome can now be carried out in a controlled manner prior to the reconstitution of infectious progeny. The described approach should be generally applicable to the mutagenesis of genomes of other large DNA viruses.
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              Control of swine pseudorabies in China: Opportunities and limitations.

              Pseudorabies (PR), also known as Aujeszky's disease (AD), is caused by pseudorabies virus (PRV) or called suid herpesvirus 1 (SuHV-1). It is an economically significant viral disease of pigs and other animals. Although the disease has been eradicated in commercial swine populations of some countries using gE-deleted vaccines and differentiating infected from vaccinated animals (DIVA) strategy, PR continues to be one of the most important diseases of pigs in many countries, particularly in regions with dense pig populations, including China. This article reviews the current situation of PR in China, including epidemiology, diagnostic assays, control strategies and challenges of the disease. PR has been endemic in most provinces of China largely due to the lack of appropriate compulsory vaccination campaigns of pigs, sufficient awareness and biosecurity measures, although gE-deleted vaccines based on the Bartha-K61 strain and regional DIVA-based eradication programs have been widely used in the past decades. Notably, since 2011, an emerging variant PRV with enhanced pathogenicity has become prevalent in vaccinated swine herds in many regions of China and the disease situation is worsening. Control and eventual eradication of PR remain a big challenge in China, and strengthened control measures based on updated DIVA strategy are urgently needed toward national eradication of PR.
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                Author and article information

                Contributors
                jcwang@263.net
                guorongli@163.com
                985654669@qq.com
                xumengwei1746109@aliyun.com
                zhisheng.wang@163.com
                lym613@hotmail.com
                617651353@qq.com
                523264193@qq.com
                houjibo@jaas.ac.cn
                Journal
                BMC Vet Res
                BMC Vet. Res
                BMC Veterinary Research
                BioMed Central (London )
                1746-6148
                7 December 2016
                7 December 2016
                2016
                : 12
                : 277
                Affiliations
                [1 ]National Research Center of Engineering and Technology for Veterinary Biologicals/Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu 210014 China
                [2 ]College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095 China
                [3 ]Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
                Article
                897
                10.1186/s12917-016-0897-z
                5142131
                27923365
                2211e344-0025-428d-bcba-d76028fc257e
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 June 2016
                : 24 November 2016
                Funding
                Funded by: the Natural Science Foundation of Jiangsu Province
                Award ID: BK20131334
                Award Recipient :
                Funded by: Program for Independence and Innovation in Agricultural Sciences of Jiangsu Province
                Award ID: CX(12)3061
                Award Recipient :
                Funded by: the Special Fund for Agro-Scientific Research in the Public Interest
                Award ID: 201303046
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Veterinary medicine
                pseudorabies virus emerging variant,ge deletion,inactivated vaccine,adjuvant,bacterial artificial chromosome,challenge protection

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