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11. 发明申请

WO2009091720A2 N-LINKED GLYCOSYLATION ALTERATION IN E1 GLYCOPROTEIN OF CLASSICAL SWINE FEVER VIRUS AND NOVEL CLASSICAL SWINE FEVER VIRUS VACCINE 审中-公开
标题翻译：经典蛇型病毒和新型经典开花病毒疫苗的E1糖蛋白中的N-连接的糖苷化改变
公开(公告)号：WO2009091720A2
公开(公告)日：2009-07-23
申请号：PCT/US2009/030824
申请日：2009-01-13
申请人： THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF AGRICULTURE , BORCA, Manuel, V. , RISATTI, Guillermo, R.
发明人： BORCA, Manuel, V. , RISATTI, Guillermo, R.
IPC分类号： C12N15/33
CPC分类号： C07H21/04 , A61K39/12 , A61K2039/5254 , A61K2039/552 , C12N7/00 , C12N2770/24334 , C12N2770/24362 , G01N33/56983 , G01N2333/183
摘要： E1, along with Ems and E2 is one of the three envelope glycoproteins of Classical Swine Fever Virus (CSFV). Our previous studies indicated that glycosylation status of either E2 or Erns strongly influence viral virulence in swine. Here, we have investigated the role of E1 glycosylation of highly virulent CSFV strain Brescia during infection in the natural host. The three putative glycosylation sites in E1 were modified by site directed mutagenesis of a CSFV Brescia infectious clone (BICv). A panel of virus mutants was obtained and used to investigate whether the removal of putative glycosylation sites in the E1 glycoprotein would affect viral virulence/pathogenesis in swine. We observed that rescue of viable virus was completely impaired by removal of all three putative glycosylation sites in E1. Single mutations of each of the E1 glycosylation sites showed that CSFV amino acid N594 (E1.N3 virus), as well the combined mutation of N500 and N513 (E1.N1N2 virus) resulted in BICv attenuation. Infection of either E1. N1N2 or E1.N3 viruses were able to efficiently protected swine from challenge with virulent BICv at 3 and 28 days post-infection. These results, along with those demonstrating the role of glycosylation of Erπs and E2, suggest that manipulation of the pattern of glycosylation could be a useful tool for development of CSF live-attenuated vaccines.
摘要翻译： E1，以及Ems和E2是经典猪瘟病毒（CSFV）的三种信封糖蛋白之一。我们以前的研究表明，E2或Erns的糖基化状态强烈影响猪的病毒毒力。在这里，我们调查了在自然宿主感染期间高毒性CSFV株Brescia的E1糖基化作用。通过CSFV布雷西亚感染性克隆（BICv）的定点诱变修饰E1中三个推定的糖基化位点。获得一组病毒突变体，用于检测E1糖蛋白中推定的糖基化位点的去除是否会影响猪的病毒毒力/发病机制。我们观察到，通过去除E1中所有三个推定的糖基化位点，完全损害了存活的病毒的拯救。每个E1糖基化位点的单突变显示CSFV氨基酸N594（E1.N3病毒）以及N500和N513（E1.N1N2病毒）的组合突变导致BICv衰减。感染E1。 N1N2或E1.N3病毒能够在感染后3和28天有效地保护猪免受毒性BICv的攻击。这些结果以及显示Erps和E2糖基化作用的结果表明，糖基化模式的操作可能是开发CSF减毒疫苗的有用工具。

12. 发明申请

WO2017114778A1 PESTIVIRUS MARKER VACCINE 审中-公开
公开(公告)号：WO2017114778A1
公开(公告)日：2017-07-06
申请号：PCT/EP2016/082537
申请日：2016-12-23
申请人： INTERVET INTERNATIONAL B.V. , INTERVET INC.
发明人： REIMANN, Ilona , KÖNIG, Patricia , BEER, Martin
IPC分类号： A61K39/12 , C07K14/005 , C12N7/04
CPC分类号： A61K39/12 , A61K2039/5252 , A61K2039/55555 , C07K14/005 , C07K2319/00 , C12N7/04 , C12N2770/24321 , C12N2770/24322 , C12N2770/24334 , C12N2770/24362 , C12N2770/24371
摘要： The present invention provides a mutant Pestivirus comprising a chimeric Erns gene, which provides the mutant Pestivirus with the capacity to evade serologic detection, but maintains good vaccine properties, and viral replication.
摘要翻译：本发明提供了包含嵌合Erns基因的突变瘟病毒，其提供了突变瘟病毒具有逃避血清学检测的能力，但保持了良好的疫苗特性和病毒复制。

13. 发明申请

WO2010135054A3 MUTATIONS IN A TOLL-LIKE RECEPTOR MOTIF IN THE NS4B OF CLASSICAL SWINE FEVER VIRUS SKIN BRESCIA INFLUENCES VIRULENCE IN SWINE 审中-公开
标题翻译：经典蛇类病毒NS4B类似感受态细胞中的突变体病毒感染西班牙血症
公开(公告)号：WO2010135054A3
公开(公告)日：2011-02-17
申请号：PCT/US2010032151
申请日：2010-04-23
申请人： US AGRICULTURE , BORCA MANUEL V , ZHU JAMES J
发明人： BORCA MANUEL V , ZHU JAMES J
IPC分类号： C12N15/40 , A61K39/12 , C07K14/08 , C12N7/01 , C12N15/63
CPC分类号： A61K39/12 , A61K2039/5254 , A61K2039/543 , A61K2039/552 , C07K14/005 , C12N7/00 , C12N2770/24322 , C12N2770/24334 , C12N2770/24362
摘要： NS4B is one of the non-structural proteins of classical swine fever virus. By using functional genetics, we have discovered, in the predicted amino acid sequence of NS4B of CSFV strain Brescia, a motif that resembles those found in the toll-like receptor (TLR) proteins, a group of host cell proteins involved in the development of anti-viral mechanisms. We have located the TLR motif in two groups of amino acid triplets at amino acid positions 2531 -3 (residues IYK) and 2566-8 (residues VGI) of the CSFV NS4B glycoprotein. We have constructed a recombinant CSFV (derived from an infectious clone containing the genetic information of the highly virulent strain Brescia) containing amino acid substitutions in the three amino acid residues at positions 2566, 2567 and 2568, where the VGI triplet has been replaced by an AAA triplet inside the NS4B glycoprotein. The obtained virus, named NS4B-VGIv, was completely attenuated in swine, showing a limited ability in spreading during the infection in vivo. Although attenuated, NS4B-VGIv efficiently protected swine from challenge with virulent BICv at 3 and 28 days post-infection.
摘要翻译： NS4B是经典猪瘟病毒的非结构蛋白之一。通过使用功能遗传学，我们已经发现，在CSFV菌株布雷西亚的NS4B的预测氨基酸序列中，类似于在toll样受体（TLR）蛋白中发现的基序，一组参与发展的宿主细胞蛋白抗病毒机制。我们将TLR基序定位在CSFV NS4B糖蛋白的氨基酸位置2531-3（残基IYK）和2566-8（残基VGI）的两组氨基酸三联体中。我们已经构建了重组CSFV（来自含有高毒力菌株Brescia的遗传信息的感染性克隆），其含有在位置2566,2567和2568处的三个氨基酸残基中的氨基酸取代，其中VGI三联体被 NS4B糖蛋白内的AAA三联体。获得的病毒NS4B-VGIv在猪中完全衰减，在体内感染期间展开的能力有限。尽管减毒，NS4B-VGIv在感染后3和28天有效地保护猪免受有毒BICv的攻击。

14. 发明申请

WO2008034857A1 PESTIVIRUS MUTANT FOR USE IN A VACCINE 审中-公开
标题翻译：生物活性物质用于疫苗
公开(公告)号：WO2008034857A1
公开(公告)日：2008-03-27
申请号：PCT/EP2007/059923
申请日：2007-09-20
申请人： INTERVET INTERNATIONAL B.V. , BEER, Martin , REIMANN, Ilona , KOENIG, Patricia
发明人： BEER, Martin , REIMANN, Ilona , KOENIG, Patricia
IPC分类号： A61K39/12 , C12N7/04
CPC分类号： C12N7/00 , A61K39/12 , A61K2039/5254 , A61K2039/552 , C12N2770/24334 , C12N2770/24362
摘要： The present invention aims at providing new pestivirus mutants for use in vaccines. The present inventors worked with pestivirus mutants containing mutations in the coding region for the Npro protein of the virus. The mutants according to the present invention are characterized in that the mutant is based on a cp strain of the virus wherein part of the gene sequence encoding the Npro region is deleted, wherein said deleted part does not encompass the coding sequence for the N-terminal twelve amino acids of the Npro protein. Preferably the pestivirus is the Bovine Viral Diarrhea Virus (BVDV). Especially for BVDV it was found that a mutant according to the invention is a safe and efficient vaccine candidate.
摘要翻译：本发明旨在提供用于疫苗的新的瘟病毒突变体。本发明人使用了在病毒的Npro蛋白的编码区中含有突变的瘟病毒突变体。根据本发明的突变体的特征在于，所述突变体是基于病毒的cp株，其中编码Npro区的基因序列的部分被缺失，其中所述缺失部分不包含N末端的编码序列 Npro蛋白的十二个氨基酸。优选地，瘟病毒是牛病毒性腹泻病毒（BVDV）。特别是对于BVDV，发现根据本发明的突变体是安全有效的疫苗候选物。

15. 发明申请

WO01039801A3 SAFE ATTENUATED BOVINE VIRAL DIARRHEA VIRUSES FOR USE IN PREGNANT COWS 审中-公开
标题翻译：安全灭火牛病毒病毒病毒
公开(公告)号：WO01039801A3
公开(公告)日：2002-02-07
申请号：PCT/EP2000/011940
申请日：2000-11-29
IPC分类号： A61K39/12 , A61P31/12 , A61P31/14 , C07K7/04 , C07K14/18 , C12N7/04 , C12N15/40
CPC分类号： C07K14/005 , A61K39/12 , A61K2039/5254 , A61K2039/543 , A61K2039/544 , A61K2039/55 , A61K2039/552 , C12N7/00 , C12N2770/24322 , C12N2770/24334 , C12N2770/24361 , C12N2770/24362 , Y10S530/826
摘要： This invention relates to the use of specifically attenuated live BVD (bovine viral diarrhea) viruses for the preparation of a vaccine for use in the prevention and/or treatment of BVDV infections in breeding stocks of cattle, pregnant cows and for fetal protection in pregnant cows.
摘要翻译：本发明涉及特异性减毒的活BVD（牛病毒性腹泻）病毒用于制备用于预防和/或治疗牛，怀孕母牛育种中的BVDV感染的疫苗和在怀孕的母牛中用于胎儿保护的用途。

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