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全球轮状病毒病的显著减少。然而，与欧洲和北美相比，非洲的疫苗效力低得多。这可能是因为这些疫苗主要是基于主要在欧洲和北美发现的轮状病毒株，而不包括在非洲流行的轮状病毒株。目标：本项目的目标是为基于在非洲流行的轮状病毒株的未来疫苗开发提供产生抗原和重组抵抗株的策略。在第一个项目期间，对莫桑比克不同轮状病毒株的实际发生情况进行了评估，表明在莫桑比克引入疫苗后，发现异常基因型组合的情况有所增加。人类和动物菌株的全基因组分析确定了多重重配的病例，表明有限的人畜共患病传播事件。选定的非洲毒株的抗原决定簇的基因组片段被用于实验，以利用反向遗传学系统产生重组轮状病毒样颗粒和重组体，这些实验基本上是成功的，但并非在所有情况下都是成功的。这包括测试嵌合基因组片段、其他骨干菌株和新的细胞培养适应方法。将对新确定的非洲菌株进行测试，以扩大抗原库。此外，将在动物中对生成的免疫剂进行抗原性检测以及使用RGS减毒轮状病毒作为新任务。将采用扩大的“一个健康”办法扩大监测范围，包括动物和环境样本，并适用于莫桑比克的特定地区。所有研究都将在德国、南非和莫桑比克的研究机构之间密切合作下进行，所有合作伙伴之间将大力转让材料、毒株和技术诀窍。成果：该项目将进一步深入了解目前在非洲流行的轮状病毒的遗传和抗原特性。将进一步开发专门为非洲大陆设计的抗原生成技术，从而产生一种新的系统，用于将新出现的轮状病毒变体快速整合到未来的疫苗制剂中。抗原性试验和病毒减毒试验将证明所产生的病毒适合用作候选疫苗。该项目还将成为非洲研究生和青年科学家培训和学术生涯发展的广泛平台。

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.