Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Coronaviruses have caused three epidemics of severe respiratory disease in humans since 2003, the last being the present COVID-19 pandemic. In each case the virus came from an animal species but was able to infect humans. In the first two epidemics, SARS and MERS, although the virus passed from an animal to humans, it did not pass readily from one human to another, limiting the size of the epidemic. SARS-CoV-2 on the other hand is readily transmitted between humans. Because the virus can mutate (change its genetic material), over time it can escape from the immune response, so that as in the case of influenza, repeated vaccination may be required to prevent severe disease, although so far the vaccines have failed to prevent virus transmission. Humans are in increasingly close contact with many animal species and the risk of further epidemics is therefore high. Pigs are one such species and can be infected with many coronaviruses including porcine respiratory coronavirus (PRCV), which causes a pneumonia similar to COVID-19. Like SARS-CoV-2 porcine coronaviruses can mutate, and recently more virulent viruses have emerged that cause economically important disease in pig herds. Pig coronaviruses have also been detected in some humans although as yet they do not appear to transmit between people. Because of the emergence of PRCV strains that cause economically important disease in pigs and because pig coronaviruses might jump to humans and cause another coronavirus epidemic, we wish to understand better how the virus infects cells in the respiratory tract, how the immune system reacts to the virus early in infection and how later on it either causes lung damage or protects against further infection. This information will be important for designing new ways to prevent or treat the disease both in pigs and humans. We will also test a novel vaccine platform which has the potential to induce very strong immune responses and possibly immune responses that could protect against widely different coronavirus. We have discovered PRCV strains that cause either severe lung disease (pneumonia) or very mild lung inflammation. We have also shown that those that cause severe disease multiply in the cells of the nose, windpipe and lungs, while those that cause mild inflammation multiply well only in the nose. Comparing the structure of these strains and making new strains by genetic manipulation will allow us to identify the parts of the virus that are important for virus entry into different cells in the respiratory tract. Part of these studies will be performed on cultured lung and tracheal (windpipe) tissues, minimising the use of live animals. To discover how the immune system responds to the virulent and innocuous viruses we will take tissues from animals infected with the two virus strains and analyse what genes are turned on one day and fourteen days after infection. This will tell us how the two virus strains programme the immune response and what sort of immune response develops after the early interaction of the viruses with the immune system. We will use a novel vaccine platform which allows the part of the virus that binds to cells (the receptor binding domain or RBD) to be displayed on a particle and internal proteins of the virus to be produced in the pig to ask several questions. First whether this vaccine induces strong and protective antibodies, second whether it can also induce protective T cells (the second protective arm of the immune response) and thirdly whether if both antibodies and T cells together are more protective than either alone. Finally using this system, we shall test whether displaying many different RBD in the vaccine induces antibodies that can protect against many different virus strains

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Combating highly pathogenic avian influenza: Novel vaccination strategies using recombinant live avian viral vaccine vectors. Avian influenza (AI) viruses (or the 'avian flu' as it is commonly called) naturally exist in wild birds such as waterfowl and shore birds where the virus is highly diverse and generally not pathogenic. These low pathogenic avian influenza (LPAI) viruses routinely cross over from the wild-bird reservoir and infect domestic poultry, frequently becoming highly pathogenic viruses (HPAI), which are extremely dangerous to commercial poultry and are occasionally fatal to humans. In the recent outbreaks of HPAI viruses of H5 and H7 subtypes in many parts of the world, including the EU, more than 200 million domestic poultry have either died or been culled, impecting huge socio-economic costs. The current epidemic of HPAI H5N1 originating from south East Asia and recently transmitted over long distances via migratory birds is unprecedented. The magnitude of risk that migratory birds are posing to the United Kingdom and other EU countries is not clear, however, there is growing evidence (recent death of migratory swan by H5N1 in Fife, Scotland) suggesting that the prevention and control of AI disease outbreak in poultry and other captive birds will be a major challenge for many years to come. To date the main strategy for controlling HPAI in domestic poultry in UK and in some other countries has been eradication of the virus by large scale culling of infected and contact flocks. However, the current world-wide epidemic has severely affected the economies of developed as well as developing countries. Therefore, for ethical, ecological and economic reasons, it is no longer considered acceptable to control and eradicate AI mainly by the mass killing of animals. As a result the European Parliament, the World Organization for Animal Health (OIE) and Food and Agriculture Organization (FAO) have allowed not only emergency vaccination, following disease outbreak, but also preventive vaccination as an additional tools for the control of AI. Currently, the available AI inactivated vaccines are produced in embryonated eggs and have several disadvantages. We propose to develop novel vaccines using some of the state of the art biotechnological tools. These will allow the administration of live viral vaccines as single injection either at hatch or into eggs before they hatch (in ovo vaccination). These new improved vaccines will be safe, effective and economical, and above all protect the commercial poultry and other domestic birds from disease and dissemination of AI viruses into the environment, consequently preventing AI virus spread, averting the looming global pandemic threat.

This project "Development of diagnostic systems, reference collections and molecular epidemiology studies for important arboviral pathogens of livestock in India" will build on established links between colleagues at The Pirbright Institute, the University of Glasgow, The John Innes Institute and the Royal Veterinary College (in the UK) with The University of Veterinary and Animal Sciences at Hisar in India, creating links with colleagues working with arboviruses in southern India. Outbreaks of arboviral diseases are a significant burden on livestock / farming communites in India. Serological data show that 21 of the 26 bluetongue virus (BTV) seroptypes exist in India, one of the highest levels of BTV diversity anywhere in the world. The severity of BT outbreaks in Indian sheep has increased significantly in recent decades, reaching 30% in some areas, possibly due to introduction of exotic strains. However, very few Indian BTV isolates have been genetically or phenotypically characterised, creating a major barrier to local validation of diagnostics and to control strategies, including development of vaccines. During the past 25 years, multiple strains of BTV and other arboviruses have emerged in Europe, possibly linked to changes in climate and global trade. However, a lack of data concerning global strain-diversity and distribution limits our ability to understand, respond to and control these events. The incomplete nature of the global database for BTV limits our ability to Identify the geographic origin of BT outbreak-strains. Similar problems exist for many endemic arboviruses in India (Myers et al 1971; Padbidri et al 2002). We will address these knowledge-gaps by isolating, identifying and characterising arboviruses from India, to study their distribution, abundance, relationships, and movements that result in disease outbreaks. The primary focus of the project is BTV, although diagnostic samples used to detect and isolate viruses, will also provide materials and potentially isolates of other arboviruses from the region. The reference collection at Pirbright provides different orbiviruses and sequence data, for development and evaluation of diagnostic assays (by RT-PCR). These assays, which identified the BTV types that invaded Europe since 1998, have become widely accepted 'front-line' tools for diagnosis, surveillance and typing of BTV around the world. However they have not yet been widely validated or deployed in India. BTV Isolates from the Pirbright collection were also used to develop / evaluate inactivated vaccine strains that successfully eradicated BTV type 8 from the UK and northern Europe . Well characterised and documented virus isolates will be generated in India, as a basis for a reference collection of 'Indian arboviruses', focussing particularly on BTV and the other orbiviruses. This will provide materials for local development of relevant vaccines (seed stocks and challenge strains) and validation / further-development of diagnostic assays for identification, detection and surveillance of these viruses on the Indian subbcontinent. Linking 'Indian-reference-collections', to the existing collection at Pirbright, will add to the global resources and our knowledge concerning these viruses. Diagnosis, isolations, sequencing, phylogenetics and virus storage will be undertaken in India, with assistance from Pirbright. Phylogenetic and evolutionary analyses will be performed at Pirbright and Glasgow. Pathology studies will be carried out at Pirbright, at the RVC and in India. The project will take advantage of recent developments in plant-based expression technologies at John Innes (JIC) (P3), to generate low-cost reagents for BTV serotyping. This will create links between plant and animal science in the UK and in India. Development of next generation serological assays will take place at JIC and Pirbright, for evaluation at Pirbright and in India.