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    • 2. 发明申请
    • DEVELOPMENT OF A MARKER FOOT AND MOUTH DISEASE VIRUS VACCINE CANDIDATE THAT IS ATTENUATED IN THE NATURAL HOST
    • 发展自然生物和自然病毒的病毒疫苗病毒候选人的发展
    • WO2012003129A3
    • 2012-07-05
    • PCT/US2011041567
    • 2011-06-23
    • US AGRICULTURERIEDER AIDA ERODRIGUEZ LUIS LHOLLISTER JASON RUDDOWLA SABENA
    • RIEDER AIDA ERODRIGUEZ LUIS LHOLLISTER JASON RUDDOWLA SABENA
    • C12N15/42A61K39/135C12N15/86C12Q1/70
    • C07K14/005A61K39/12A61K39/135A61K2039/5252A61K2039/5254A61K2039/552A61K2039/55566C12N7/00C12N2770/32121C12N2770/32122C12N2770/32134C12N2770/32151C12N2770/32162C12N2770/32163C12N2770/32171C12Q1/701G01N33/56983G01N2469/10
    • We have generated novel molecularly marked FMDV A24LL3DYR and A24LL3BPVKV3DYR vaccine candidates. The mutant viruses contain a deletion of the leader coding region (LL) rendering the virus attenuated in vivo and negative antigenic markers introduced in one or both of the viral non-structural 3Dpol and 3B proteins. Mutations were introduced into MAb F32-44 epitope in FMDV A24Cruzeiro spanning residues H27N31 in 3Dpol protein to obtain the homologous amino acid sequence of bovine rhinitis virus type B (BRV-2, Y27R31). Mutations in 3B consisted of a deletion of 3B1 and a mutation in 3B2 (RQKP->PVKV, found in BRV-2) that abolishes reactivity with MAb F8B. These attenuated marker viruses provide safe alternatives for FMD vaccine manufacturing. The vaccine platform includes unique restriction endonuclease sites for easy swapping of capsid proteins for different FMDV subtypes and serotypes. Chimeric viruses were produced to contain the capsid of distantly related type A/Turkey/06 or Asia type FMDV: Asia1-A24LL3BPVKV3DYR and A/Turkey/06 -A24LL3BPVKV3DYR. A24LL3DYR and A24LL3BPVKV3DYR mutant viruses produced no signs of FMD and no shedding of virulent virus in cattle. No clinical signs of disease or fever were observed and no transmission to in-contact animals was detected in pigs inoculated with live A24LL3DYR or the chimeric A-Turkey/06-A24LL3BPVKV3DYR or Asia1-A24LL3BPVKV3DYR viruses. Cattle immunized with chemically inactivated A24LL3DYR and A24LL3BPVKV3DYRvaccine candidates showed an efficacy comparable to a polyvalent commercial FMDV vaccine and protected 100% the animals from challenge with parental virus. The single and double marked-FMDV vaccine candidates used in conjunction with a cELISA provide a suitable target for DIVA companion tests.
    • 我们生成了新型分子标记的FMDV A24LL3DYR和A24LL3BPVKV3DYR疫苗候选物。 突变体病毒包含导致体内减毒的前导编码区(LL)的缺失和引入病毒非结构3Dpol和3B蛋白之一或两者的阴性抗原标记。 在3Dpol蛋白中将突变引入跨越H27N31的FMDV A24Cruzeiro的MAb F32-44表位,得到B型牛鼻炎病毒(BRV-2,Y27R31)的同源氨基酸序列。 3B中的突变包括3B1缺失和3B2突变(RQKP-> PVKV,在BRV-2中发现),其消除与MAb F8B的反应性。 这些减毒标记病毒为口蹄疫疫苗生产提供了安全的替代方案。 疫苗平台包括独特的限制性内切核酸酶位点,可以方便地交换不同FMDV亚型和血清型的衣壳蛋白。 生产嵌合病毒以包含远离相关类型A / Turkey / 06或亚洲型FMDV:Asia1-A24LL3BPVKV3DYR和A / Turkey / 06 -A24LL3BPVKV3DYR的衣壳。 A24LL3DYR和A24LL3BPVKV3DYR突变体病毒在牛中没有产生FMD的迹象,也没有产生毒性病毒的脱落。 没有观察到疾病或发烧的临床症状,并且在用活A24LL3DYR或嵌合A-Turkey / 06-A24LL3BPVKV3DYR或Asia1-A24LL3BPVKV3DYR病毒接种的猪中未检测到接触动物的传播。 用化学灭活的A24LL3DYR和A24LL3BPVKV3DYRvaccine候选物免疫的牛显示出与多价商业FMDV疫苗相当的功效,并保护100%的动物免受亲代病毒攻击。 与cELISA一起使用的单和双标记FMDV疫苗候选者为DIVA伴侣测试提供了合适的目标。
    • 4. 发明申请
    • DEVELOPMENT OF A MARKER FOOT AND MOUTH DISEASE VIRUS VACCINE CANDIDATE THAT IS ATTENUATED IN THE NATURAL HOST
    • 在天然宿主中降解标记基因和口腔病毒疫苗候选株的研制
    • WO2012003129A2
    • 2012-01-05
    • PCT/US2011/041567
    • 2011-06-23
    • THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF AGRICULTURERIEDER, Aida E.RODRIGUEZ, Luis L.HOLLISTER, Jason R.UDDOWLA, Sabena
    • RIEDER, Aida E.RODRIGUEZ, Luis L.HOLLISTER, Jason R.UDDOWLA, Sabena
    • C12N15/42A61K39/135C12N15/86C12Q1/70
    • C07K14/005A61K39/12A61K39/135A61K2039/5252A61K2039/5254A61K2039/552A61K2039/55566C12N7/00C12N2770/32121C12N2770/32122C12N2770/32134C12N2770/32151C12N2770/32162C12N2770/32163C12N2770/32171C12Q1/701G01N33/56983G01N2469/10
    • We have generated novel molecularly marked FMDV A 24 LL3D YR and A 24 LL3B PVKV 3D YR vaccine candidates. The mutant viruses contain a deletion of the leader coding region (LL) rendering the virus attenuated in vivo and negative antigenic markers introduced in one or both of the viral non-structural 3D pol and 3B proteins. Mutations were introduced into MAb F32-44 epitope in FMDV A24Cruzeiro spanning residues H 27 N 31 in 3 Dpol protein to obtain the homologous amino acid sequence of bovine rhinitis virus type B (BRV-2, Y 27 R 31 ). Mutations in 3B consisted of a deletion of 3B 1 and a mutation in 3B 2 (RQKP->PVKV, found in BRV-2) that abolishes reactivity with MAb F8B. These attenuated marker viruses provide safe alternatives for FMD vaccine manufacturing. The vaccine platform includes unique restriction endonuclease sites for easy swapping of capsid proteins for different FMDV subtypes and serotypes. Chimeric viruses were produced to contain the capsid of distantly related type A/Turkey/06 or Asia type FMDV: Asia1-A 24 LL3B PVKV 3D YR and A/Turkey/06 -A 24 LL3B PVKV 3D YR . A2 4 LL3D YR and A 24 LL3B PVKV 3D YR mutant viruses produced no signs of FMD and no shedding of virulent virus in cattle. No clinical signs of disease or fever were observed and no transmission to in-contact animals was detected in pigs inoculated with live A24LL3DYR or the chimeric A-Turkey/06-A 24 LL3B PVKV 3D YR or Asia1-A 24 LL3B PVKV 3D YR viruses. Cattle immunized with chemically inactivated A24LL3DYR and A 24 LL3B PVKV 3D YR vaccine candidates showed an efficacy comparable to a polyvalent commercial FMDV vaccine and protected 100% the animals from challenge with parental virus. The single and double marked-FMDV vaccine candidates used in conjunction with a cELISA provide a suitable target for DIVA companion tests.
    • 我们已经产生了新的分子标记的FMDV A 24 LL3DYYR和A 24 LL3B PVKV, 3D> YR疫苗候选物。 突变病毒含有导致病毒在体内减毒的前导编码区(LL)缺失和在病毒非结构3D pol和3B蛋白之一或两者中引入的阴性抗原标志物。 将突变导入3'Dpol蛋白中FMDV A24Cruzeiro跨越残基H27N31的MAb F32-44表位中以获得同源氨基酸序列 的B型牛鼻炎病毒(BRV-2,Y27R31)。 3B中的突变由3B1的缺失和3B2(RQKP-&gt; PVKV,在BRV-2中发现)中的突变组成,其消除了与MAb F8B的反应性。 这些减毒标记病毒为口蹄疫疫苗制造提供了安全的选择。 该疫苗平台包含独特的限制性内切酶位点,以便于更换不同FMDV亚型和血清型的衣壳蛋白。 产生嵌合病毒以包含远缘相关的A / Turkey / 06型或亚洲型FMDV的衣壳:Asia1-A24 LL3B-PVKV 3D-YR 和A /土耳其/ 06 -A <24> LL3B YR 。 A2 4 LL3DYYR和A244 LL3B PVKV 3DYR突变体病毒产生无 口蹄疫的迹象以及牛群中没有病毒流出。 在接种活A24LL3DYR或嵌合A-Turkey / 06-A24 LL3B PVKV的猪中没有观察到疾病或发热的临床体征并且未检测到接触性动物的传播。 亚型YR亚型或Asia1-A24型LL3B亚型PVKV 3DYR亚型病毒。 用化学灭活的A24LL3DYR和A24LL3BVVKV 3DYR候选疫苗候选物免疫接种的牛表现出与多价商业FMDV疫苗相当的功效并且保护了100% 来自亲代病毒攻击的动物。 与cELISA结合使用的单标记和双标记FMDV候选疫苗为DIVA伴侣测试提供了合适的目标。