US-UK BBSRC-NIFA Collab: Control of emerging bunyaviruses

Arboviruses are viruses transmitted by arthropod vectors such as mosquitoes, biting flies or ticks, and can infect both man and livestock. Bunyaviruses are one group of arboviruses and include the well-known Rift Valley fever virus that causes devastating epidemics among sheep and cattle in Africa, and a new virus, Schmallenberg virus, that appeared in Europe in 2011 and rapidly spread throughout the continent causing abortions, stillbirths and malformations of calves and lambs. In order to prepare for future outbreaks of bunyavirus disease we need to understand why certain insect vectors are able to spread a particular virus whereas others cannot, and whether local insects would be capable to supporting transmission of an introduced virus. This will be addressed by infecting different mosquito and midge species with different viruses, and determining the factors involved in a successful transmission. Should a new outbreak occur, we need to be able to respond rapidly with vaccines to contain the disease. We will use our ability to genetically modify viruses to produce weakened viruses that can no longer cause disease but are able to induce protective antibodies in the host animal that will preventive subsequent infection. The candidate vaccines will be assessed for their efficacy in sheep and will establish general principles for the development of further vaccines in the future.

The overall goals of this collaborative project are to increase our understanding of bunyavirus-vector interactions, and to generate new live-attenuated vaccines that can be rapidly deployed to protect against emergence of new bunyavirus disease. Bunyaviruses include the mosquito transmitted Rift Valley fever, that is a continual threat for emergence outside of Africa, and the midge transmitted Schmallenberg virus, a new virus that emerged in Europe in 2011 and which quickly spread. Using selected bunyaviruses, the roles of viral proteins in the ability to infect and be transmitted by different mosquito and midge species will be studied. The effect of the insect innate immune response in shaping the nature of the infection will be analysed in detail. Exploiting reverse genetics, recombinant attenuated viruses, lacking the nonstructural NSs and NSm proteins, will be tested for their efficacy to protect against homologous wild type virus challenge in sheep. These studies will lay the foundation for a new vaccine platform against any new bunyavirus that will emerge in the future.

Who might benefit from this research?
The immediate beneficiary of this research will be the national and international academic community in the direct field of this research and more broadly, through the acquisition of new knowledge. The general public will also be a direct beneficiary of this work. The results of this project will be of interest to animal health pharmaceutical companies and also to national, international and inter-governmental policy makers, including bodies such as the Animal World Health Organisation (OIE) who have responsibility for monitoring and controlling the spread of animal viruses.

How might they benefit from this research?
This project aspires to develop a vaccine platform for the rapid generation of new vaccines against emerging bunyaviruses. If successful, this technology will significantly enhance our readiness and preparedness to respond to outbreaks of emerging and re-emerging bunyaviruses in animals. Therefore, the outcomes of the proposed work are likely to have potential for commercial exploitation that will directly benefit animal health pharmaceutical companies. We enjoy established collaborations with both Pifzer and Merial Animal Health, both of which are supported by BBSRC through CASE studentships and an Industrial Partnership award. These partnerships are a route through which to manage and maximize the findings of our research and to explore commercial exploitation of the results of this project to realize these impacts.

Exploitation of our findings by the pharmaceutical industry is likely to have a direct impact on the UK economy by reducing morbidity and mortality in economically significant farmed animals and therefore be of benefit to the general public. The availability of a bluetongue virus vaccine has been estimated to have saved the UK economy £485M and 10,000 jobs. Therefore we will endeavour to disseminate our findings to the non-scientific community to explain our work and why it is important. CVR staff have a strong track record of engagement with the general public, and our activities to inspire school children to study science include workshops and science fairs, and student placements in research laboratories.

The ready availability of effective vaccines targeting emerging and re-emerging bunyaviruses can be expected to be of significant benefit to policy makers with responsibility for the control and containment of animal viruses, nationally and internationally. The CVR is an OIE Collaborating Centre and we will use our links to OIE to share the outcomes of this work and provide regular updates. This project is also likely to come under the umbrella of the Global Uncertainties Programme of projects and so we will also take advantage of opportunities for 'enhanced impact' through discussion with Dr Tristram Riley-Smith, the Global Uncertainties Programme's External Champion.

The development and application of new techniques, generation of new knowledge and exposure to different research environments will also benefit the career development of the Research Assistant to be employed on this project. In addition to acquiring new scientific expertise, the research assistant will also contribute to project management of this study, will assist in managing the project budget, provide support and training to other members of the group and be responsible for presenting results generated from this work in the form of written manuscripts and oral conference presentations. Development of these transferable skills will enhance the future employability of the individual, irrespective of the career path they chose to pursue.