Development of a vaccination strategy for the control of malignant catarrhal fever

制定控制恶性卡他热的疫苗接种策略

• 批准号: BB/H009035/1
• 负责人: Sarah Cleaveland
• 金额: $ 22.38万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH009035%2F1
• 关键词: Development; vaccination; strategy; control; malignant

This proposal aims to further develop and refine our recent breakthrough of an immunisation strategy for the control of malignant catarrhal fever (MCF) by increasing the magnitude and duration of immunity through improved adjuvancy (compounds given along with virus antigens that help direct the type of immune response to an infectious agent and improve its magnitude and duration - all important for a good vaccine) and testing the potential vaccine in field trials in Tanzania where MCF is a problem. Malignant catarrhal fever (MCF) is a fatal disease of cattle, deer, bison and pigs, caused by a group of viruses (herpesviruses) including ovine herpesvirus-2 and alcelaphine herpesvirus-1. These viruses infect their natural hosts efficiently (sheep for OvHV-2 and wildebeest for AlHV-1), causing no apparent disease, but in the disease-susceptible animals, MCF is usually fatal and consequently has a profound affect on animal welfare and production. The virus is transmitted by aerosol or by contact and most lambs or wildebeest calves are infected shortly after birth and are capable of then infecting susceptible cattle. There is no vaccine currently available for MCF, but we have recently developed a potential vaccine that works well in experimental studies. The effect of AlHV-1 MCF on pastoralist communities in sub-Saharan Africa is profound, with social, economic and welfare impact. In two studies of MCF in Tanzania and Kenya, incidence in studied areas was found to be 6% and 10% respectively. The high rate of cattle death meant that MCF was rated as the most important disease risk in areas with wildebeest contact. Field trials in Tanzania are essential to determine the efficacy of the alcelaphine herpesvirus-1 (AlHV-1) MCF vaccine and will inform further refinement of the vaccine as necessary. It is important to determine the contribution of the different components of an immune response that will protect affected cattle. Although there is a strong correlation between virus-neutralising antibody and protection, we need to determine whether cell-mediated immunity (CMI) including cytotoxic T cell activity (CTL) is involved or not in protection. Furthermore, we need to identify virus component antigens that stimulate protective immune responses in cattle. This will allow vaccine development for ovine herpesvirus-2 (OvHV-2, a highly genetically-related virus to AlHV-1) MCF, which is a problem not only in Africa but worldwide where natural carrier animals and disease-susceptible animals mix. This dual approach is important as there is more likely to be a commercial uptake of an AlHV-1 and OvHV-2 MCF vaccine than either one singly. This study will use defined new generation adjuvant compounds to improve the current AlHV-1 MCF vaccine and test this in field trials in Tanzania. For very little extra effort, we can identify the protective virus component antigens of AlHV-1 and use the equivalent OvHV-2 ones to attempt a vaccine to OvHV-2 MCF. This increases the chances of commercial uptake of an MCF vaccine. The expected principal outcome of this work wil be implementation of a vaccine disease control strategy to have an impact on animal mortality due to MCF and improvement of quality of life of pastoralists and farmers within 5 years of the conclusion of this project.

这项建议旨在进一步发展和完善我们最近在控制恶性卡他热（MCF）免疫策略方面的突破，通过提高免疫力来增加免疫力的强度和持续时间。（与病毒抗原一起沿着给予的化合物，有助于指导对感染因子的免疫反应类型，并改善其强度和持续时间-所有这些对于良好的疫苗都很重要）并在坦桑尼亚的田间试验中测试潜在的疫苗，那里的MCF是一个问题。恶性卡他热（malignant catarrhal fever，MCF）是由绵羊疱疹病毒2型（ovine herpesvirus-2）和阿卡拉芬疱疹病毒1型（alcelaphine herpesvirus-1）引起的牛、鹿、野牛和猪的一种致死性疾病。这些病毒有效地感染其天然宿主（绵羊为OvHV-2，角马为AlHV-1），不引起明显的疾病，但在疾病易感动物中，MCF通常是致命的，因此对动物福利和生产有深远的影响。该病毒通过气溶胶或接触传播，大多数羔羊或牛羚小牛在出生后不久就被感染，然后能够感染易感牛。目前还没有针对MCF的疫苗，但我们最近开发了一种在实验研究中效果良好的潜在疫苗。AlHV-1 MCF对撒哈拉以南非洲牧民社区的影响是深远的，具有社会、经济和福利影响。在坦桑尼亚和肯尼亚进行的两项MCF研究中，发现研究地区的发病率分别为6%和10%。牛的高死亡率意味着MCF被评为与牛羚接触地区最重要的疾病风险。坦桑尼亚的田间试验对于确定alcelaphine疱疹病毒-1（AlHV-1）MCF疫苗的有效性至关重要，并将在必要时为疫苗的进一步改进提供信息。重要的是要确定免疫反应的不同组成部分的贡献，将保护受影响的牛。虽然病毒中和抗体和保护之间有很强的相关性，但我们需要确定包括细胞毒性T细胞活性（CTL）在内的细胞介导的免疫（CMI）是否参与保护。此外，我们还需要鉴定能刺激牛保护性免疫反应的病毒组分抗原。这将允许开发针对绵羊疱疹病毒-2（OvHV-2，一种与AlHV-1高度遗传相关的病毒）MCF的疫苗，这不仅是非洲的问题，也是世界范围内的问题，其中天然载体动物和疾病易感动物混合。这种双重方法很重要，因为AlHV-1和OvHV-2 MCF疫苗比任何一种单独使用更有可能被商业化。这项研究将使用确定的新一代佐剂化合物来改进目前的AlHV-1 MCF疫苗，并在坦桑尼亚的田间试验中进行测试。只需付出很少的努力，我们就可以鉴定出AlHV-1的保护性病毒组分抗原，并使用等效的OvHV-2抗原来尝试OvHV-2 MCF的疫苗。这增加了MCF疫苗商业化的机会。这项工作的预期主要成果将是实施一项疫苗疾病控制战略，以在本项目结束后5年内降低由MCF引起的动物死亡率，并改善牧民和农民的生活质量。

项目成果

Ecology and conservation: contributions to One Health.

生态与保护：对“同一个健康”的贡献。

• DOI: 10.20506/rst.33.2.2307
• 发表时间: 2014
• 期刊: Revue scientifique et technique (International Office of Epizootics)
• 作者: Cleaveland S

Animal Health and Biodiversity: Preparing for the Future

动物健康和生物多样性：为未来做好准备

• 发表时间: 2011
• 作者: Cleaveland, S.

Alcelaphine Herpesvirus-1 (Malignant Catarrhal Fever Virus) in Wildebeest Placenta: Genetic Variation of ORF50 and A9.5 Alleles.

叶贝斯特胎盘中的Alcelaphine疱疹病毒-1（恶性CATARRHAL热病毒）：ORF50和A9.5等位基因的遗传变异。

• DOI: 10.1371/journal.pone.0124121
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Lankester F;Lugelo A;Mnyambwa N;Ndabigaye A;Keyyu J;Kazwala R;Grant DM;Relf V;Haig DM;Cleaveland S;Russell GC
• 通讯作者: Russell GC

The economic impact of malignant catarrhal fever on pastoralist livelihoods.

• DOI: 10.1371/journal.pone.0116059
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Lankester F;Lugelo A;Kazwala R;Keyyu J;Cleaveland S;Yoder J
• 通讯作者: Yoder J

A field vaccine trial in Tanzania demonstrates partial protection against malignant catarrhal fever in cattle.

• DOI: 10.1016/j.vaccine.2015.12.009
• 发表时间: 2016-02-03
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Lankester F;Russell GC;Lugelo A;Ndabigaye A;Mnyambwa N;Keyyu J;Kazwala R;Grant D;Percival A;Deane D;Haig DM;Cleaveland S
• 通讯作者: Cleaveland S