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

05/2018–04/2021

This third-party funded project is conducted in the framework of the BfR research programme on exposure estimation and the assessment of biological risks.

DFG grant number: JO369/5-1

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Project description:

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 efficacy is considerably lower in Africa as compared to Europe and North America. One reason for the variable vaccine efficacy may be the circulation of different rotavirus field strains. As the vaccines are mainly based on rotavirus strains predominantly found in Europe and North America, they may exhibit a lower efficacy against the specific rotavirus strains circulating in Africa. 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. As rotavirus field strains are often difficult to isolate in cell culture, a novel reverse genetics system will be applied for rapid generation of specific replication-competent rotavirus reassortants containing antigenic determinants of African field strains. Both systems will further be optimized during the project to enable rapid and targeted generation of antigens and vaccine strains in future. Initial characterisation of the generated antigens and viruses will be performed. 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. By application of two complementary strategies for antigen production, a development of inactivated as well as live vaccines would be possible. In addition, novel systems for targeted generation of rotavirus reassortants and virus-like particles will be optimized, which may enable the rapid integration of newly emerging rotavirus variants into future vaccine formulations. The project will also serve as a broad platform for training and development of academic careers for postgraduate students and junior scientists from Africa.

Project partners:

• Charité - Universitätsmedizin, Germany
• University of the Free State, South Africa
• Ministério da Saúde, Mozambique
• North-West University, South Africa

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