Antigens and Reassortant Strains for Rotaviruses Circulating in Africa

背景：轮状病毒感染是全球幼儿严重胃肠炎的主要原因。危及生命的疾病主要发生在非洲和亚洲的发展中国家。减毒活疫苗的使用导致轮状病毒病在全球范围内显著减少。然而，与欧洲和北美相比，非洲的疫苗效力要低得多。这可能是因为疫苗主要基于主要在欧洲和北美发现的轮状病毒毒株，不包括在非洲传播的轮状病毒毒株。目标：该项目的目标是为未来基于在非洲传播的轮状病毒毒株生成抗原和重组重配毒株提供策略。成就：在第一个项目阶段，评估了莫桑比克不同轮状病毒毒株的实际发生情况，表明莫桑比克疫苗引入后，异常基因组合的检测有所增加。对人类和动物毒株的全基因组分析发现了多种重新组合的病例，表明人畜共患传播事件有限。利用选定的非洲毒株的抗原决定簇的基因组片段，使用反向遗传学系统(RGS)进行了实验，以产生重组轮状病毒样颗粒和重配子，主要是成功的，但并不是在所有情况下都是如此。计划调查：开发的技术将进一步优化，以克服在第一个项目期间变得明显的限制。这包括对嵌合基因组片段、其他骨干菌株和新的细胞培养适应方法的测试。将对新确定的非洲毒株进行测试，以扩大抗原库。此外，动物体内产生的重组体的抗原性测试以及使用RGS对轮状病毒的减毒作用将作为新的任务包括在内。将在莫桑比克的特定地区扩大监测范围，采用包括动物和环境样本在内的扩展的“一个健康”方法。所有调查将在德国、南非和莫桑比克的研究机构之间密切合作进行，并在所有合作伙伴之间密集转让材料、毒株和技术诀窍。输出：该项目将进一步深入了解目前在非洲传播的轮状病毒的遗传和抗原性。将进一步开发专门为非洲大陆设计的抗原生成技术，从而形成一种新的系统，将新出现的轮状病毒变种快速整合到未来的疫苗配方中。抗原性测试和病毒减毒试验将证明产生的病毒适合用作疫苗候选。该项目还将成为培训和发展非洲研究生和初级科学家学术事业的广泛平台。

Background: Rotavirus infections are the main cause of severe gastroenteritis in young children worldwide. Life-threatening disease mainly occurs in developing countries in Africa and Asia. The use of live-attenuated vaccines led to a significant decrease of rotavirus disease worldwide. However, the vaccine efficacy is considerably lower in Africa as compared to Europe and North America. This could be because the vaccines are mainly based on rotavirus strains predominantly found in Europe and North America and do not include strains circulating in Africa.Goal: The goal of this project is to provide strategies for the generation of antigens and recombinant reassortant strains for future vaccine development based on rotavirus strains circulating in Africa.Achievements: In the first project period, the actual occurrence of different rotavirus strains was assessed in Mozambique, indicating an increased detection of unusual genotype combinations after vaccine introduction in Mozambique. Whole genome analysis of human and animal strains identified cases of multiple reassortment suggesting limited zoonotic transmission events. Genome segments of the antigenic determinants of selected African strains were used in experiments to generate recombinant rotavirus-like particles and reassortants using a reverse genetics system (RGS), which were mainly successful, but not in all cases.Planned investigations: The developed technologies will be further optimized in order to overcome the limitations that became obvious during the first project period. This includes the testing of chimeric genome segments, other backbone strains and novel cell culture adaption approaches. Newly determined African strains will be tested to broaden the antigenic repertoire. In addition, antigenicity testing of the generated reassortants in animals as well as the attenuation of rotaviruses using RGS will be included as new tasks. Surveillance will be expanded using an extended One-Health approach including animal and environmental samples, applied to specific regions in Mozambique. All investigations will be conducted in close collaboration between research institutions in Germany, South Africa and Mozambique and with intensive transfer of materials, strains and technical know-how between all partners.Output: The project will give further insights into the genetic and antigenic properties of rotaviruses currently circulating in Africa. The techniques for generation of antigens, which are specifically designed for the African continent, will be further developed resulting in a novel system for rapid integration of newly emerging rotavirus variants into future vaccine formulations. The antigenicity testing and virus attenuation trials will prove the suitability of the generated viruses for use as vaccine candidates. The project will also serve as a broad platform for training and development of academic careers for postgraduate students and junior scientists from Africa.