Evaluation of modified Vaccinia Ankara-based vaccines against foot-and-mouth disease serotype A24 in cattle

Steigerwald Robin; Brake David A.; Barrera Jose; Schutta Christopher J.; Kalla Markus; Wennier Sonia T.; Volkmann Ariane; Hurtle William; Clark Benjamin A.; Zurita Mariceny; Pisano Melia; Kamicker Barbara J.; Puckette Michael C.; Rasmussen Max V; Neilan John G.

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Evaluation of modified Vaccinia Ankara-based vaccines against foot-and-mouth disease serotype A24 in cattle

机译：对牛口腔疾病血管型A24的改性痘苗血管基疫苗的评价

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To prepare foot-and-mouth disease (FMD) recombinant vaccines in response to newly emerging FMD virus (FMDV) field strains, we evaluated Modified Vaccinia virus Ankara-Bavarian Nordic (MVA-BN (R)) as an FMD vaccine vector platform. The MVA-BN vector has the capacity to carry and express numerous foreign genes and thereby has the potential to encode antigens from multiple FMDV strains. Moreover, this vector has an extensive safety record in humans. All MVA-BN-FMD constructs expressed the FMDV A24 Cruzeiro P1 capsid polyprotein as antigen and the FMDV 3C protease required for processing of the polyprotein. Because the FMDV wild-type 3C protease is detrimental to mammalian cells, one of four FMDV 3C protease variants were utilized: wild-type, or one of three previously reported mutants intended to dampen protease activity (C142T, C142L) or to increase specificity and thereby reduce adverse effects (L127P). These 3C coding sequences were expressed under the control of different promoters selected to reduce 3C protease expression. Four MVA-BN-FMD constructs were evaluated in vitro for acceptable vector stability, FMDV P1 polyprotein expression, processing, and the potential for vaccine scale-up production. Two MVA-BN FMD constructs met the in vitro selection criteria to qualify for clinical studies: MVA-mBN3606 (carrying a C142T mutant 3C protease and an HIV frameshift for reduced expression) and MVA-mBN386B (carrying a L127P mutant 3C protease). Both vaccines were safe in cattle and elicited low to moderate serum neutralization titers to FMDV following multiple dose administrations. Following FMDV homologous challenge, both vaccines conferred 100% protection against clinical FMD and viremia using single dose or prime-boost immunization regimens. The MVA-BN FMD vaccine platform was capable of differentiating infected from vaccinated animals (DIVA). The demonstration of the successful application of MVA-BN as an FMD vaccine vector provides a platform for further FMD vaccine development against more epidemiologically relevant FMDV strains. Published by Elsevier Ltd.

机译：为了响应新出现的FMD病毒（FMDV）场菌株，为新出现的FMD病毒（FMD）疫苗进行准备，我们评估了改性的痘苗病毒Ankara-Bavarian Nordic（MVA-BN（R））作为FMD疫苗载体平台。 MVA-BN载体具有携带和表达许多外源基因的能力，从而具有从多个FMDV菌株中编码抗原的可能性。此外，该载体在人类中具有广泛的安全记录。所有MVA-BN-FMD构建体表达了FMDV A24 Cruzeiro P1衣壳聚丙烯作为抗原和处理聚丙烯所需的FMDV 3C蛋白酶。由于FMDV野生型3C蛋白酶对哺乳动物细胞有害，因此使用了四种FMDV 3C蛋白酶变体中的一种：野生型，或三个先前报告的突变体中的一种，旨在抑制蛋白酶活性（C142T，C142L）或增加特异性从而减少不良反应（L127P）。这些3C编码序列在选择以减少3C蛋白酶体表达的不同启动子的控制下表达。在体外评估四种MVA-BN-FMD构建体，用于可接受的载体稳定性，FMDV P1多蛋白表达，加工以及疫苗放大生产的可能性。两个MVA-BN FMD构建体满足了鉴定临床研究的体外选择标准：MVA-MBN3606（携带C142T突变体3C蛋白酶和减少表达的HIV架构）和MVA-MBN386B（携带L127P突变体3C蛋白酶）。在多剂量施用后，两种疫苗在牛中是安全的，并引发低至血清中和滴度至FMDV。在FMDV同源挑战之后，使用单剂量或素升压免疫方案，疫苗赋予临床FMD和病毒血症的100％保护。 MVA-BN FMD疫苗平台能够区分从接种疫苗的动物（DIVA）感染。作为FMD疫苗载体的成功应用MVA-BN的证明提供了一种用于进一步的FMD疫苗开发的平台，可针对更多流行病学相关的FMDV菌株。 elsevier有限公司出版

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来源
《Vaccine》 |2020年第4期|共10页
作者
Steigerwald Robin; Brake David A.; Barrera Jose; Schutta Christopher J.; Kalla Markus; Wennier Sonia T.; Volkmann Ariane; Hurtle William; Clark Benjamin A.; Zurita Mariceny; Pisano Melia; Kamicker Barbara J.; Puckette Michael C.; Rasmussen Max V; Neilan John G.;
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作者单位

Bavarian Nordic GmbH Fraunhoferstr 13 D-82152 Martinsried Germany;

BioQuest Associates LLC Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

Leidos Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

US Dept Homeland Secur Sci &

Technol Directorate Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

Bavarian Nordic GmbH Fraunhoferstr 13 D-82152 Martinsried Germany;

Bavarian Nordic GmbH Fraunhoferstr 13 D-82152 Martinsried Germany;

Bavarian Nordic GmbH Fraunhoferstr 13 D-82152 Martinsried Germany;

US Dept Homeland Secur Sci &

Technol Directorate Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

Leidos Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

Leidos Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

Leidos Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

Leidos Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

US Dept Homeland Secur Sci &

Technol Directorate Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

US Dept Homeland Secur Sci &

Technol Directorate Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

US Dept Homeland Secur Sci &

Technol Directorate Plum Isl Anim Dis Ctr POB 848 Greenport NY 11944 USA;

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原文格式 PDF
正文语种 eng
中图分类医学免疫学;
关键词
Efficacy; Foot-and-mouth disease virus; MVA vectored vaccine; FMDV; DIVA;

机译：疗效;口蹄疫病毒;MVA矢量疫苗;FMDV;DIVA;

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专利

1. Evaluation of modified Vaccinia Ankara-based vaccines against foot-and-mouth disease serotype A24 in cattle [J] . Steigerwald Robin, Brake David A., Barrera Jose, Vaccine . 2020,第4期

机译：对牛口腔疾病血管型A24的改性痘苗血管基疫苗的评价
2. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge [J] . Schutta Christopher, Barrera Jose, Pisano Melia, Vaccine . 2016,第27期

机译：腺病毒载体牛口蹄疫病毒血清型A24亚单位疫苗在牛中的多重功效研究
3. Efficacy of an adenovirus-vectored foot-and-mouth disease virus serotype A subunit vaccine in cattle using a direct contact transmission model [J] . John G. Neilan, Christopher Schutta, José Barrera, BMC Veterinary Research . 2018,第1期

机译：使用直接接触传播模型的腺病毒载体口蹄疫病毒血清型A亚单位疫苗在牛中的功效
4. FOOT-AND-MOUTH DISEASE VIRUS VACCINES: DEVELOPMENT OF A MARKER, MULTIEPITOPE SUBUNIT VACCINE [C] . Marvin J. Grubman Annual Meeting of the United States Animal Health Association . 2008

机译：口蹄疫病毒疫苗：发育标志物，多皮岩亚单位疫苗
5. Immunochemical and biological characterization of neutralizing and cross-reactive murine monoclonal antibodies to foot-and-mouth disease virus A24 Cruzeiro. [D] . Bratic, Jelena. 2006

机译：抗口蹄疫病毒A24 Cruzeiro的中和和交叉反应性鼠单克隆抗体的免疫化学和生物学特性。
6. Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle [O] . Yan Xiao, Hong-Ying Chen, Yuzhou Wang, 2016

机译：在大肠杆菌中大规模生产口蹄疫病毒（亚洲1型血清型）VLP疫苗和牛的保护力评估
7. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge [O] . Schutta Christopher, Barrera José, Pisano Melia, 2016

机译：腺病毒载体牛口蹄疫病毒血清型A24亚单位疫苗在牛中的多重功效研究

Evaluation of modified Vaccinia Ankara-based vaccines against foot-and-mouth disease serotype A24 in cattle

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