Antigens and Reassortant Strains for Rotaviruses Circulating in Africa (AfRota)

Rotavirus infections are the main cause of severe gastroenteritis in young children worldwide. Life-threatening disease courses are mainly observed in developing countries in Africa and Asia. The recent introduction of two live-attenuated vaccines led to a significant decrease of severe rotavirus disease worldwide. However, the vaccine efficacyClose dialogefficacyPositive Predictive ValueTo glossary is considerably lower in Africa as compared to Europe and North America. One reason for the variable vaccine efficacyClose dialogefficacyPositive Predictive ValueTo glossary may be the circulation of different rotavirus field strains. 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. The investigations will be conducted in close collaborations between different research institutes in Germany, South Africa and Mozambique and intensive transfer of materials, strains and technical know-how between all partners is planned. Rotavirus field samples will be collected at different sites from southern Africa and the identified strains will be characterized by whole genome sequencing and cell culture isolation trials. Antigenic determinants for selected strains will be produced by generation of recombinant rotavirus-like particles, which usually represent excellent non-replicating vaccine antigens, in insect cells. In addition, a novel reverse genetics system will be applied for rapid generation of specific replication-competent rotavirus reassortants containing antigenic determinants of African field strains. The project will give insights into the genetic and antigenic properties of rotaviruses currently circulating in southern Africa. Based in this information, it will provide strategies for the generation of candidate vaccine antigens specifically designed for the African continent, which might prove to be more efficient than the currently used global vaccine strains.

Rotaviruses  are distributed in humans and animals and are transmitted by direct contact or contaminated drinking water or food. 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 efficacyClose dialogefficacyPositive Predictive ValueTo glossary is considerably lower in Africa as compared to Europe and North America. The goal of this project was therefore to provide strategies for the generation of antigens and recombinant reassortant strains for future vaccine development based on rotavirus strains circulating in Africa. In the project, the actual occurrence of different rotavirus strains was assessed in Mozambique. By this, a broad variety of different strains were detected. Especially, virus types that were not present in the actual vaccines tended to spread in the analyzed time-period. A closer look at selected human and animal strains by whole genome analyses indicated that they are constantly evolving and exchanging genetic material. In addition, reassortant strains with new genome segment combinations were identified. Using a newly developed reverse genetics system, vialble reassortants containing antigens of the African strains could be generated in the laboratory and charaterized in cell culture. However, for some of the tested strains, no viable viruses could be generated and studies elucidating the reasons behind this failure have been initiated. In parallel, tools for the generation of non-replicating virus-like particles derived from  rotavirus capsid proteins were initially developed. The results indicate that specific rotavirus strains circulate and evolve in Subsaharan Africa, which are not fully covered by the actually available vaccines. The application of the developed reverse genetics system enables the rapid generation of viable rotavirus strains, which share the antigenic characteristics of circulating African rotavirus field strains. These could possibly by used in future for production of novel vaccines specifically disigned for the African continent, where currently most of the fatal rotavirus infections occur.