Exploiting novel African swine fever virus virulence factors and a porcine macrophage cell line to develop a live attenuated vaccine
利用新型非洲猪瘟病毒毒力因子和猪巨噬细胞系开发减毒活疫苗
基本信息
- 批准号:BB/V007947/1
- 负责人:
- 金额:$ 47.5万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2021
- 资助国家:英国
- 起止时间:2021 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
African swine fever (ASF) is a deadly disease of pigs and wild boar that has a very high socio-economic impact. The rapid spread of ASF in China and other Asian countries since 2018 has resulted in death or destruction of more than 7 million pigs, reducing the Chinese pig herd by about 40% and the global herd by 25%. As pork is the most widely consumed source of protein globally, this has had serious consequences on food prices and supply of protein for human consumption. Combined with continuing ASF spread in Africa and Europe, this represents an unprecedented threat to global food security. In Europe 1408 outbreaks in domestic pigs and 6003 detections in wild boars have been reported since July 2019. In S. E Asia ASF has spread to 11 countries and in Africa ASF is present in almost all countries south of the Sahara. There is no vaccine for ASF limiting disease control. A vaccine is urgently needed to limit ASF outbreaks in affected countries and prevent further global spread.This project brings together a cutting-edge academic/industry partnership including two academic partners, The Pirbright Institute and Plymouth University and a leading international veterinary vaccine company, Zoetis, to rapidly progress vaccine development by exploiting our new research discoveries. The complexity of this large DNA virus (ASFV), which codes for up to 170 proteins, has hindered vaccine development. It is recognised that the fastest way to develop a vaccine is to produce a weakened ASFV (a live attenuated vaccine or LAV) which does not cause disease in pigs but induces an immune response that protects them from disease caused by subsequent infection with the deadly virus. We showed previously (7, BBSRC funded) that deleting ASFV genes that aren't required for the virus to replicate in cells but have important roles in helping the virus to evade the host's defences in infected animals, can produce LAV candidates. Now, we have identified novel genes, which, when deleted, can eliminate any disease signs caused by the LAV and induce good levels of protection against infection with the deadly virus. However, moderate disease signs and virus replication are observed after challenge. In this project we will improve on these results by deleting different combinations of these novel virulence factor genes to produce LAV strains causing only mild or no clinical signs following immunisation. We aim to protect 80 to 100% of pigs from disease and prevent the replication of the deadly virus so that it doesn't spread to other pigs. The lack of a cell line to grow the LAV candidates to high titres and in large volumes has prevented commercial production of this type of ASFV vaccine. Now we have developed a cell line that closely resembles the macrophage cells that ASFV naturally replicates in. Infection of this cell line produces high amounts of ASFV. In this project, the growth of this cell line will be optimized and scaled up for commercial production. The production of the selected LAV vaccine strain will also be scaled up using the cell line and pre-licensing tests of the vaccine completed. We will also use this cell line to investigate how ASFV modulates the functions of its target cell, the macrophage, thus avoiding detection and activation of the host's defences. The project will deliver high-quality science as well as providing a major step forward to commercial vaccines for ASFV.
非洲猪瘟(ASF)是猪和野猪的致命疾病,具有非常高的社会经济影响。自2018年以来,非洲猪瘟在中国和其他亚洲国家的快速传播已导致超过700万头猪死亡或销毁,使中国猪群减少约40%,全球猪群减少25%。由于猪肉是全球消费最广泛的蛋白质来源,这对粮食价格和人类消费的蛋白质供应产生了严重后果。加上非洲猪瘟在非洲和欧洲的持续传播,这对全球粮食安全构成了前所未有的威胁。自2019年7月以来,欧洲已报告1408起家猪疫情和6003起野猪疫情。In S.非洲猪瘟已经蔓延到11个国家,在非洲,撒哈拉以南的几乎所有国家都有非洲猪瘟。目前还没有ASF限制性疾病控制的疫苗。该项目汇集了包括两个学术合作伙伴Pirbright研究所和普利茅斯大学以及领先的国际兽医疫苗公司硕腾公司在内的尖端学术/行业合作伙伴关系,通过利用我们的新研究发现快速推进疫苗开发。这种编码多达170种蛋白质的大型DNA病毒(ASFV)的复杂性阻碍了疫苗的开发。人们认识到,开发疫苗的最快方法是生产一种弱化的ASFV(一种减毒活疫苗或LAV),这种疫苗不会引起猪的疾病,但会诱导免疫反应,保护猪免受随后感染致命病毒引起的疾病。我们以前表明(7,BBSRC资助),删除ASFV基因,这些基因不是病毒在细胞中复制所必需的,但在帮助病毒逃避感染动物的宿主防御方面具有重要作用,可以产生LAV候选人。现在,我们已经确定了新的基因,当删除时,可以消除LAV引起的任何疾病症状,并诱导良好的保护水平,防止致命病毒的感染。然而,攻毒后观察到中度疾病体征和病毒复制。在本项目中,我们将通过删除这些新毒力因子基因的不同组合来改进这些结果,以产生在免疫后仅引起轻微或无临床体征的LAV毒株。我们的目标是保护80%到100%的猪不受疾病的影响,并防止致命病毒的复制,使其不会传播给其他猪。缺乏使LAV候选物生长至高滴度和大量的细胞系已经阻止了这种类型的ASFV疫苗的商业生产。现在,我们已经开发出一种细胞系,它与ASFV自然复制的巨噬细胞非常相似。该细胞系的感染产生大量的ASFV。在该项目中,将优化该细胞系的生长并扩大规模用于商业生产。选定LAV疫苗株的生产也将使用已完成的疫苗细胞系和许可前试验扩大规模。我们还将使用该细胞系来研究ASFV如何调节其靶细胞巨噬细胞的功能,从而避免检测和激活宿主的防御。该项目将提供高质量的科学,并为ASFV的商业疫苗迈出重要一步。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A protective multiple gene-deleted African swine fever virus genotype II, Georgia 2007/1, expressing a modified non-haemadsorbing CD2v protein.
- DOI:10.1080/22221751.2023.2265661
- 发表时间:2023-12
- 期刊:
- 影响因子:13.2
- 作者:Rathakrishnan, Anusyah;Reis, Ana L.;Petrovan, Vlad;Goatley, Lynnette C.;Moffat, Katy;Lui, Yuan;Vuong, Mai T.;Ikemizu, Shinji;Davis, Simon J.;Dixon, Linda K.
- 通讯作者:Dixon, Linda K.
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Linda Dixon其他文献
In vitro and emin vivo/em antiviral activity of nucleoside analogue cHPMPC against African swine fever virus replication
- DOI:
10.1016/j.antiviral.2022.105433 - 发表时间:
2022-12-01 - 期刊:
- 影响因子:4.000
- 作者:
Leah V. Goulding;Eleonóra Kiss;Lynnette Goatley;Robert Vrancken;Nesya E.J. Goris;Linda Dixon - 通讯作者:
Linda Dixon
Linda Dixon的其他文献
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{{ truncateString('Linda Dixon', 18)}}的其他基金
Exploring transcription of a large DNA virus of importance for global food security
探索对全球粮食安全具有重要意义的大型 DNA 病毒的转录
- 批准号:
BB/X015424/1 - 财政年份:2023
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
Taiwan Partnering Award: Investigation of proteins involved in African swine fever virus entry for vaccine development
台湾合作奖:研究与非洲猪瘟病毒进入相关的蛋白质以用于疫苗开发
- 批准号:
BB/T019832/1 - 财政年份:2021
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
African swine fever outbreak containment strategy using small-molecule antiviral drugs
使用小分子抗病毒药物遏制非洲猪瘟疫情的策略
- 批准号:
BB/S015256/1 - 财政年份:2019
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
Further development of an African swine fever virus live attenuated vaccine
非洲猪瘟病毒减毒活疫苗的进一步研制
- 批准号:
BB/L004267/1 - 财政年份:2014
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
US Partnering Award: Using bioinformatics to predict and understand virus-host interactions to improve ASFV vaccines, therapeutics and diagnostics.
美国合作奖:利用生物信息学预测和了解病毒与宿主的相互作用,以改进 ASFV 疫苗、治疗和诊断。
- 批准号:
BB/L026562/1 - 财政年份:2014
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
EPIZONE European Research Group Meeting: "Viruses on the move"
EPIZONE 欧洲研究小组会议:“移动中的病毒”
- 批准号:
BB/J019704/1 - 财政年份:2012
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
African swine fever virus: Understanding virus host interactions and improving control strategies
非洲猪瘟病毒:了解病毒宿主相互作用并改进控制策略
- 批准号:
BB/I024739/1 - 财政年份:2011
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
Exploiting African swine fever virus surface proteins to develop rapid diagnostic tests and understand virus host interactions
利用非洲猪瘟病毒表面蛋白开发快速诊断测试并了解病毒宿主相互作用
- 批准号:
BB/H008969/1 - 财政年份:2010
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
Outpacing infectious diseases: African swine fever virus vaccine development
超越传染病:非洲猪瘟病毒疫苗的开发
- 批准号:
BB/G530468/1 - 财政年份:2009
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
Mechanism of action of an african swine fever virus virulence factor. THIS GRANT IS A SUPPLEMENTATION TO GRANT REF BB/E021239
非洲猪瘟病毒毒力因子的作用机制。
- 批准号:
BB/H53116X/1 - 财政年份:2009
- 资助金额:
$ 47.5万 - 项目类别:
Research Grant
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