Molecular epidemiology network for promotion and support of delivery of life vaccines against Theileria parva and Theileria annulata infection in Eastern and Northern Africa

分子流行病学网络，促进和支持在东非和北非提供针对细小泰勒虫和环状泰勒虫感染的生命疫苗

• 批准号: 234548756
• 负责人: Professor Dr. Peter-Henning Clausen
• 金额: --
• 依托单位: International Livestock Research Institute
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/234548756?language=en
• 关键词: Molecular; epidemiology; network; promotion; support

Tropical theileriosis (Theileria annulata) and East Coast fever (ECF, caused by T. parva) are major constraints for development of livestock where the diseases are endemic. Currently, management of theileriosis relies on chemotherapy, tick control using acaricides and to a certain degree immunization. After nearly a century of acaricide utilization, it is now clear that this alone cannot provide a sustainable solution to the control of theileriosis. Infection and treatment vaccination (ITM) for control of ECF is an alternative control method involving inoculation with live T. parva sporozoites and simultaneous treatment with a long-acting dose of oxytetracycline. The recent first successful large scale deployment of the orginal trivalent Muguga cocktail (TV) version of ITM without apparent breakthrough infections in pastoralist systems in Tanzania has renewed the desire for more extensive deployment. We are currently supporting ITM deployment by using markers for the genetic composition of stabilates comprising the TV to assess if vaccination induces a persistent, tick transmissible infection (carrier state) with foreign parasite genotpyes that could result in enhanced disease problems. We propose to continue our DFG collaboration to set the stage for wider deployment of ITM. In particular, we will address the issue of to what extent the gene pools of cattle and African buffalo-derived T. parva populations are separate, both in Tanzania and in the new target regions for deployment in Southern Sudan and Central Uganda. In addition, we also propose to bridge the host genetics gap in the development of broadly protective multi-epitope subunit vaccines against T. parva and further explore a vaccination strategy based on T. parva-infected B-lymphocytes. A live vaccine for T. annulata based on inoculation of attenuated schizont-infected leukocytes has been established in Egypt and Sudan in phase 2. The aim of the project is to: (i) ascertain whether attenuated vaccines can protect animals from tropical theileriosis under field conditions in Egypt and Sudan, (ii) assess whether attenuated vaccines can be improved by combining them with subunit vaccines, (iii) assess attenuation of candidate T. annulata culture vaccines based on the up- and down-regulation of attenuation markers identified in phase 2, (iv) achieve an evidence-based statement of the design, development and safety criteria of attenuated live vaccines.Of particular interest is the situation in Southern Sudan where we have recently demonstrated for the first time the geographical spread of T. parva towards the north of South Sudan (Marcellino et al, 2016). The latter is particular interesting since it makes South Sudan unique as the only country in the world where T. annulata and T. parva both occur and there is preliminary data suggesting co-existence in certain herds. We propose to assess the impact of this co-existence on the outcome of immunization trials.

热带泰勒虫病（Theileria annulata）和东海岸热（ECF，由 T. parva 引起）是这些疾病流行的牲畜发展的主要限制因素。目前，泰勒虫病的治疗依赖于化疗、使用杀螨剂控制蜱虫以及一定程度的免疫接种。经过近一个世纪的杀螨剂使用后，现在很明显，仅靠这一点无法为控制泰勒虫病提供可持续的解决方案。用于控制 ECF 的感染和治疗疫苗接种 (ITM) 是一种替代控制方法，包括接种活的细小毛细线虫子孢子并同时使用长效剂量的土霉素进行治疗。最近首次成功大规模部署原始三价 Muguga 鸡尾酒 (TV) 版本的 ITM，在坦桑尼亚的牧区系统中没有出现明显的突破性感染，这再次激发了更广泛部署的愿望。我们目前正在支持 ITM 部署，方法是使用包含 TV 的稳定物的遗传组成标记来评估疫苗接种是否会诱导具有外来寄生虫基因型的持续性蜱传播感染（携带者状态），从而可能导致疾病问题加剧。我们建议继续与 DFG 合作，为更广泛的 ITM 部署奠定基础。特别是，我们将解决坦桑尼亚以及苏丹南部和乌干达中部部署的新目标地区的牛和非洲水牛衍生的细小蝽种群的基因库在多大程度上是分开的问题。此外，我们还建议在针对细小毛虫的广泛保护性多表位亚单位疫苗的开发中弥合宿主遗传学差距，并进一步探索基于细毛细虫感染的B淋巴细胞的疫苗接种策略。埃及和苏丹已在第二阶段建立了一种基于接种减毒裂殖体感染白细胞的环带T. annulata活疫苗。该项目的目的是：（i）确定减毒疫苗是否可以在埃及和苏丹的野外条件下保护动物免受热带泰勒虫病，（ii）评估减毒疫苗是否可以通过与亚单位疫苗结合来改进， (iii) 根据第 2 阶段确定的减毒标记的上调和下调来评估候选 T. annulata 培养疫苗的减毒情况，(iv) 实现减毒活疫苗的设计、开发和安全标准的循证声明。特别令人感兴趣的是苏丹南部的情况，我们最近首次证明了 T. parva 向南苏丹北部的地理传播（Marcellino 等人， 2016）。后者特别有趣，因为它使南苏丹成为世界上唯一一个同时存在环纹瘿虫和细叶瘿虫的国家，并且有初步数据表明某些种群中共存。我们建议评估这种共存对免疫试验结果的影响。

项目成果

The protection afforded to cattle immunized with Theileria annulata infected cell line is enhanced by subunit vaccine candidate TaSP.

候选亚单位疫苗 TaSP 增强了对环形泰勒虫感染细胞系免疫的牛的保护作用

• DOI: 10.1111/tbed.13374
• 发表时间: 2020
• 期刊: Transboundary and emerging diseases
• 影响因子: 4.3
• 作者: Saaid A;Salih D;Elhaj L;Abdalla M;Baumann M;Obara I;Ahmed J;Clausen PH;El Hussein A
• 通讯作者: El Hussein A

Antigen gene and variable number tandem repeat (VNTR) diversity in Theileria parva parasites from Ankole cattle in south-western Uganda: Evidence for conservation in antigen gene sequences combined with extensive polymorphism at VNTR loci.

乌干达西南部 Ankole 牛的细小泰勒虫寄生虫的抗原基因和可变数目串联重复序列 (VNTR) 多样性：抗原基因序列保守性与 VNTR 位点广泛多态性相结合的证据

• DOI: 10.1111/tbed.13311
• 发表时间: 2020
• 期刊: Transboundary and emerging diseases
• 影响因子: 4.3
• 作者: Nanteza A;Obara I;Kasaija P;Mwega E;Kabi F;Salih DA;Njahira M;Njuguna J;Odongo D;Bishop RP;Skilton RA;Ahmed J;Clausen PH;Lubega GW
• 通讯作者: Lubega GW

First detection of Theileria parva in cattle from Cameroon in the absence of the main tick vector Rhipicephalus appendiculatus

• DOI: 10.1111/tbed.13425
• 发表时间: 2020-03-01
• 期刊: TRANSBOUNDARY AND EMERGING DISEASES
• 影响因子: 4.3
• 作者: Silatsa, Barberine A.;Simo, Gustave;Pelle, Roger
• 通讯作者: Pelle, Roger

Towards wider and more efficient deployment of live vaccines for control of Theileria parva and Theileria annulata infections in cattle in eastern, central and northern Africa.

更广泛、更有效地部署活疫苗，以控制东部、中部和北部非洲牛的细小泰勒虫和环状泰勒虫感染

• DOI: 10.1111/tbed.13359
• 发表时间: 2020
• 期刊: Transboundary and emerging diseases
• 影响因子: 4.3
• 作者: Obara I;Ahmed J;Bishop R;Clausen PH
• 通讯作者: Clausen PH