AniMAb: Establishing a monoclonal antibody platform to interrogate animal antibody responses to inform rational design of veterinary vaccines

AniMAb：建立单克隆抗体平台来探究动物抗体反应，为兽用疫苗的合理设计提供信息

• 批准号: BB/M018636/1
• 负责人: Jonathan Ball
• 金额: $ 19.03万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM018636%2F1
• 关键词: AniMAb; Establishing; monoclonal; antibody; platform

Many animal [and human] infections are difficult to control through vaccination because they are caused by viruses, bacteria and parasites that are able to out-run the immune system by constantly mutating. All-too-often, the antibody and killer cells that the body makes to fight off infection target these mutating regions of the microbe. However, we suspect that microbes also possess much more conserved regions that could be targeted by vaccines, and therefore if we could identify these conserved regions we would be able to make a vaccine that would work against lots of different strains. In this project, we will develop a system that will allow us to isolate monoclonal antibodies from animals, in the first instance cows. Having this technology will allow us to dissect out the antibody response that cows make to vaccines or to natural infection. We can then screen these antibodies to find those that are able to recognise and kill different strains of a microbe, e.g. a virus. We can then work out what part of the microbe these antibodies target and use this information to make better vaccines. Importantly, we can expand this technology to inform vaccine design for all species of animals.

许多动物[和人类]感染很难通过疫苗接种来控制，因为它们是由病毒、细菌和寄生虫引起的，这些病毒、细菌和寄生虫能够通过不断变异超越免疫系统。通常，人体为抵抗感染而产生的抗体和杀伤细胞会针对微生物的这些突变区域。然而，我们怀疑微生物还拥有更多可以成为疫苗目标的保守区域，因此，如果我们能够识别这些保守区域，我们就能够制造出一种针对许多不同菌株的疫苗。在这个项目中，我们将开发一个系统，使我们能够从动物（首先是奶牛）中分离出单克隆抗体。拥有这项技术将使我们能够剖析奶牛对疫苗或自然感染产生的抗体反应。然后我们可以筛选这些抗体，找到那些能够识别和杀死不同菌株的微生物的抗体，例如细菌。一种病毒。然后我们可以找出这些抗体针对微生物的哪个部分，并利用这些信息来制造更好的疫苗。重要的是，我们可以扩展这项技术，为所有动物物种的疫苗设计提供信息。

项目成果

Broad neutralization of hepatitis C virus-resistant variants by Civacir hepatitis C immunoglobulin.

• DOI: 10.1002/hep.28767
• 发表时间: 2016-11
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Tawar RG;Heydmann L;Bach C;Schüttrumpf J;Chavan S;King BJ;McClure CP;Ball JK;Pessaux P;Habersetzer F;Bartenschlager R;Zeisel MB;Baumert TF
• 通讯作者: Baumert TF

Novel functional hepatitis C virus glycoprotein isolates identified using an optimized viral pseudotype entry assay.

• DOI: 10.1099/jgv.0.000537
• 发表时间: 2016-09
• 期刊: The Journal of general virology
• 作者: Urbanowicz RA;McClure CP;King B;Mason CP;Ball JK;Tarr AW
• 通讯作者: Tarr AW

Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

• DOI: 10.1016/j.virol.2016.02.003
• 发表时间: 2016-05
• 期刊: Virology
• 影响因子: 3.7
• 作者: R. B. Ferns;A. Tarr;S. Hué;R. Urbanowicz;C. P. McClure;R. Gilson;J. Ball;E. Nastouli;J. Garson;D. Pillay

Human Adaptation of Ebola Virus during the West African Outbreak.

• DOI: 10.1016/j.cell.2016.10.013
• 发表时间: 2016-11-03
• 期刊: CELL
• 影响因子: 64.5
• 作者: Urbanowicz, Richard A.;McClure, C. Patrick;Sakuntabhai, Anavaj;Sall, Amadou A.;Kobinger, Gary;Mueller, Marcel A.;Holmes, Edward C.;Rey, Felix A.;Simon-Loriere, Etienne;Ball, Jonathan K.
• 通讯作者: Ball, Jonathan K.

Targeting a host-cell entry factor barricades antiviral-resistant HCV variants from on-therapy breakthrough in human-liver mice.

靶向宿主细胞进入因子可阻止人肝小鼠治疗中突破性的抗病毒耐药丙型肝炎病毒变异体。

• DOI: 10.1136/gutjnl-2014-309045
• 发表时间: 2016
• 期刊: Gut
• 影响因子: 24.5
• 作者: Vercauteren K