Using a 'Vaccinomics' Approach to Characterise FMDV Evolution under Vaccine Selection

使用“疫苗组学”方法来表征疫苗选择下的 FMDV 演变

• 批准号: 1646570
• 金额: --
• 依托单位: University of Surrey
• 依托单位国家: 英国
• 项目类别: Studentship
• 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=studentship-1646570
• 关键词: Using; Vaccinomics; Approach; Characterise; FMDV

Contributing to food security and our economy, animal health is a strategic priority of the BBSRC. Our work on the development of successful animal-disease intervention strategies by producing more effective vaccines is a powerful strategy to protect our livestock, with viruses such as rinderpest already successfully eradicated. Foot-and-mouth disease virus (FMDV) has significant socio-economic effects on livestock and its eradication/outbreak control through vaccinations is of prime importance. Many RNA viruses such as FMDV exist as heterogeneous populations known as quasispecies, comprising related but non-identical genomes. Such complexity is due to their high replication rate, large population size and error-prone replication with current estimates predicting one nucleotide change occurring during each cycle of virus replication (Klein et al, 2009). Such evolutionary plasticity places significant limitations upon the strategies for the design ofefficacious vaccines that can protect against a wide range of constantly changing circulating field strains. Moreover, minor variants of FMDV, that may have an important role in transmission and quasispecies evolution with potentially serious effects on vaccine stability and efficacy (mixed-population vaccines), remain uncharacterised. Systematic investigations into the factors that effect FMDV vaccine quality in terms of characterising minor variants, quasispecies dynamics, heterogeneity and invoking a host-response are therefore critical in establishing a robust vaccination regime against FMDV outbreaks.High throughput technologies and large-scale datasets such as genomics, transcriptomics and proteomics are increasingly being exploited within vaccine development and vaccine safety research, hence the term Vaccinomics (Luciani et al, 2012). Here we employ high-throughput sequencing to address three objectives: 1. Accurately and rapidly obtain whole genomesequences (WGS) of different FMDV strains from different geographical regions to further understanding of the molecular and evolutionary mechanisms employed by FMDV quasispecies that drive immune escape and contribute to viral persistence or carrier states. (i.e. working towards an FMDV prevention program) 2. Detect and characterise minority variants and escape mutants (as low as 0.1%) to understand the heterogeneity of vaccines and the effects that this has on vaccine quality (i.e. working towards an improved/more robust vaccination program). 3. Determine the host's transcriptomic response to FMDV vaccinations, to understand the interactions between host and pathogen/vaccination that are important for providing protection (i.e. working towards a refined vaccination program). High-throughput technologies will also be used to characterise and assess aspects of vaccine quality criteria (i.e. homogeneity of seed lots and adventitious pathogens).

为促进粮食安全和我们的经济，动物健康是BBSRC的战略优先事项。我们通过生产更有效的疫苗制定成功的动物疾病干预战略的工作是保护我们牲畜的有力战略，牛瘟等病毒已经成功根除。口蹄疫病毒（FMDV）对牲畜有重大的社会经济影响，通过接种疫苗根除/控制疫情至关重要。许多RNA病毒如口蹄疫病毒作为异质群体存在，称为准种，包括相关但不相同的基因组。这种复杂性是由于它们的高复制率、大群体大小和易错复制，目前的估计预测在病毒复制的每个周期期间发生一个核苷酸变化（Klein等人，2009）。这种进化的可塑性对设计有效疫苗的策略造成了很大的限制，这些疫苗可以保护人们免受大范围不断变化的田间流行毒株的侵害。此外，FMDV的微小变异体可能在传播和准种进化中发挥重要作用，对疫苗稳定性和有效性（混合群体疫苗）具有潜在的严重影响，但仍未得到鉴定。因此，系统地研究影响口蹄疫疫苗质量的因素，如微小变异、准种动态、异质性和宿主反应等，对于建立一个强大的疫苗接种机制以预防口蹄疫爆发至关重要。高通量技术和大规模数据集，如基因组学、转录组学和蛋白质组学，越来越多地被用于疫苗开发和疫苗安全性研究，因此有了“疫苗组学”一词（Luciani等人，2012）。在这里，我们采用高通量测序来解决三个目标：1。准确、快速地获得来自不同地理区域的不同FMDV毒株的全基因组序列（WGS），以进一步了解FMDV准种驱动免疫逃逸并促成病毒持久性或携带状态的分子和进化机制。(i.e.致力于FMDV预防计划）2.检测和鉴定少数变异体和逃逸突变体（低至0.1%），以了解疫苗的异质性及其对疫苗质量的影响（即致力于改进/更稳健的疫苗接种计划）。3.确定宿主对FMDV疫苗接种的转录组反应，以了解宿主和病原体/疫苗接种之间的相互作用，这对提供保护很重要（即努力制定完善的疫苗接种计划）。高通量技术还将用于检验和评估疫苗质量标准的各个方面（即种子批和外源病原体的均一性）。

项目成果

Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus.

• DOI: 10.3390/v14081820
• 发表时间: 2022-08-19
• 期刊: Viruses

A Systematic Evaluation of High-Throughput Sequencing Approaches to Identify Low-Frequency Single Nucleotide Variants in Viral Populations.

• DOI: 10.3390/v12101187
• 发表时间: 2020-10-20
• 期刊: Viruses
• 作者: King DJ;Freimanis G;Lasecka-Dykes L;Asfor A;Ribeca P;Waters R;King DP;Laing E
• 通讯作者: Laing E

Efficacy of a high-potency multivalent foot-and-mouth disease virus vaccine in cattle against heterologous challenge with a field virus from the emerging A/ASIA/G-VII lineage.

• DOI: 10.1016/j.vaccine.2018.02.016
• 发表时间: 2018-03-27
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Waters R;Ludi AB;Fowler VL;Wilsden G;Browning C;Gubbins S;Statham B;Bin-Tarif A;Mioulet V;King DJ;Colenutt C;Brown E;Hudelet P;King DP
• 通讯作者: King DP