Application of next generation phage display technology to development of a Differentiation of Infected from Vaccinated Animals (DIVA) strategy

应用下一代噬菌体展示技术开发区分感染者与疫苗接种动物 (DIVA) 策略

基本信息

批准号：
BB/M018822/1
负责人：
Janet Daly
金额：
$ 14.89万
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%2FM018822%2F1
关键词：
Application next generation phage display

项目摘要

Incursions of hitherto exotic or unknown viral diseases affecting livestock animals appear to have been increasing in frequency in recent years. Climate change and increasing globalisation are thought to be contributing factors; therefore it seems likely that this trend will continue. The most recent example was the emergence of Schmallenberg virus, which causes birth defects and abortions in cattle and sheep. Diagnostic tests, including assays to measure antibodies against the virus, were rapidly developed and an inactivated whole virus vaccine was granted an emergency license in a relatively short time-frame. However, economic losses as a result of Schmallenberg virus have been substantial, particularly as a result of countries that have remained free of the disease imposing trade restrictions on animals (and products from them such as semen) from affected regions. A differentiation of infected from vaccinated animals (DIVA) strategy refers to an approach in which a diagnostic assay detects antibodies that are present in naturally-infected animals but not in animals that have been vaccinated. Such a test allows demonstration that animals are free of infection even if they have been vaccinated to protect them from disease. In the case of some virus diseases, the lack of such a strategy can mean that international trade restrictions and killing animals are seen as the best option for controlling an outbreak. It is difficult to distinguish between antibodies raised to an inactivated whole virus vaccine because all of the same structural virus components that generate an antibody response in infection are present. However, we hypothesise that the chemical treatments used to inactivate the virus in the preparation of vaccines will modify the structure of viral proteins and lead to subtle changes in the antibody repertoire. Next generation phage display (NGPD) is a powerful emerging technology that we propose to apply in a novel way to identify any regions that represent linear epitopes or mimotopes of conformational epitopes of the virus proteins that differ sufficiently to allow antibodies from naturally-infected cows to be distinguished from those from vaccinated cows. These peptides could then be applied in a DIVA test. Schmallenberg virus has been chosen to provide 'proof-of-principle'. If successful, the approach could be applied to other emerging viruses that pose a threat to UK livestock now or in the future allowing a rapid response to include not only an inactivated vaccine but an accompanying DIVA test thereby providing a comprehensive control strategy without any associated product export restrictions.

近年来，迄今为止，影响牲畜动物的迄今为止的异国情调或未知病毒疾病的入侵似乎在增加。气候变化和日益全球化被认为是促成因素。因此，这种趋势似乎会继续下去。最近的例子是施马伦堡病毒的出现，该病毒导致牛和绵羊的先天缺陷和堕胎。诊断测试（包括测量针对该病毒的抗体的测定方法）迅速开发，并在相对较短的时间框架中授予了全部病毒疫苗的灭活。但是，由于施马伦伯格病毒的经济损失是巨大的，特别是由于仍然没有疾病的国家对动物（以及来自它们的精液的产物）施加贸易限制的国家。与接种疫苗的动物（DIVA）策略之间感染的分化是指诊断测定法检测到自然感染动物但未接种疫苗的动物中存在的抗体的方法。这样的测试允许证明动物没有感染，即使已接种疫苗以保护它们免受疾病的侵害。在某些病毒疾病的情况下，缺乏这种策略可能意味着国际贸易限制和杀死动物被视为控制爆发的最佳选择。很难区分对整个病毒疫苗灭活的抗体，因为存在于感染中产生抗体反应的所有相同的结构病毒成分。但是，我们假设用于在疫苗制备中灭活病毒的化学处理将改变病毒蛋白的结构，并导致抗体库的细微变化。下一代噬菌体展示（NGPD）是一种强大的新兴技术，我们建议以一种新颖的方式应用，以识别代表病毒蛋白的线性表位或构象表位的任何区域，这些区域的构型表位构象表位与从疫苗接种的母牛中分开的抗体以允许自然感染的奶牛的抗体有足够的抗体。然后可以将这些肽应用于DIVA测试中。 Schmallenberg病毒已被选为提供“原理证明”。如果成功的话，该方法可以应用于其他新兴病毒，这些病毒现在或将来对英国牲畜构成威胁，允许快速反应不仅包括灭活的疫苗，还包括随附的Diva测试，从而提供了无需任何相关产品出口的全面控制策略。