Antigens and Reassortant Strains for Rotaviruses Circulating in Africa

• Applicant: Professor Dr. Reimar Johne
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 317234633

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.

• DFG Programme: Research Grants
• International Connection: Mozambique, South Africa
• Co-Investigator: Professor Dr. Jörg Hofmann
• Cooperation Partners: Dr. Lizanne Meiring; Dr. Martin Nyaga; Professor Dr. Christiaan Potgieter
• International Co-Applicants: Professorin Nilsa De Deus, Ph.D.; Professorin Alberdina van Dijk, Ph.D.; Dr. Hester O' Neill