Funded Projects - Round 1
1) Development of immunological tools for monitoring the immune response of Nile tilapia
Professor Kim Thompson (Moredun Research Institute), Professor Sachdev S. Sidhu (University of Toronto), Professor Alexandra Adams (University of Stirling), Dr. Alasdair Nisbet (Moredun Research Institute), Dr. Hoang Nguyen (Vietnam National University, Ho Chi Minh City), Dr. Nguyen Ngoc Phuoc (Hue University of Agriculture and Forestry, Vietnam) & Professor Ruth Zadoks (University of Glasgow)
Aquaculture is the fastest growing animal food production sector globally. Fish are an import source of protein and as such aquaculture has great potential to play a key role in future food security programmes. Because of their rapid growth and high protein content, tilapia is an attractive species for aquaculture, reaching harvest size after only 6-7 months; tilapia are now in fact the second most farmed species after carp. They are farmed in many low and middle-income countries (LMIC) and provide an important source of revenue for many low income families. Disease in tilapia culture is associated with intensification of the farming system, and both bacterial and viral diseases are severely impacting on the expansion of tilapia farming; in particular Streptococcus spp. There is increasing concern about the use of antibiotics to control disease outbreaks and attention is focusing on the use of vaccination for disease control. Vaccination exposes fish to a non-infectious dose of the pathogen, so when they come into contact with the pathogen at a later date, memory cells of their immune system stimulate a response to combat the disease. We need a better understanding of how tilapia respond to infection and vaccination to be able to develop and formulate effective vaccine products for tilapia. We currently have few reagents available for investigating the immune response of tilapia. Through a collaboration of scientists in Vietnam, Canada and the UK, we plan to develop and apply novel tools (synthetic antibodies) for studying the immune response of this important aquaculture species, using Streptococcus agalactiae as our infection model. Synthetic antibodies are made in the laboratory, unlike conventional antibodies which are produce in animals, thus eliminating the need to use animals to make these reagents. This work will ultimately lead to the development of more effective strategies for managing disease in tilapia aquaculture systems.
2) Low-cost thermostabilisation of a Rift Valley Fever vaccine for veterinary use
Dr. George Warimwe (KEMRI-Wellcome Trust Research Programme), Dr. Alexander D. Douglas (Jenner Institute) & Dr. Michael J. Francis (Biovacc Consulting Ltd)
Vaccines are among the most cost-effective public health interventions ever developed. However, many of the currently available products require refrigeration in order to maintain their viability and ability to elicit a protective immune response in humans or animals. This requirement for a ‘cold chain’ has major cost implications, and remains a major challenge in the deployment of vaccines in resource-poor settings where uninterrupted supply of electricity to maintain a cold chain in fridges is unavailable. In this project we aim to develop and optimise a low-cost method of formulating vaccines to obviate the need for refrigeration. We will exploit the known properties of certain sugars, trehalose and sucrose, to thermostabilise live viruses when slowly desiccated on to fibrous membranes with minimal loss in viability. We will adapt an existing method to make it suitable for stabilisation of very low cost veterinary vaccine formulations, which are not purified to the same extent as human formulations. To demonstrate the utility of this new method, we will thermostabilise an advanced candidate vaccine in development for Rift Valley Fever (ChAdOx1 RVF) in humans and animals, and evaluate its viability and ability to elicit an immune response in mice following storage at low (4C), medium (20C) and high (45C) temperatures for 6 months. If successful, the thermostable ChAdOx1 RVF will be further developed for commercialisation, both for the human and veterinary indications. The data generated in this project will also be useful in informing thermostabilisation protocols for other veterinary (and human) vaccines.
3) A single dose vectored Taenia solium vaccine
Professor Adrian Hill (Jenner Institute), Professor Marshall Lightowlers (University of Melbourne) & Dr. Bryan Charleston (The Pirbright Institute)
Taenia solium is the aetiological agent of neurocysticercosis in humans and is associated with a high frequency of epilepsy in endemic areas. Pigs are the almost exclusive natural animal intermediate host for T. solium and immunisation of pigs offers the opportunity for disease prevention. Despite the general difficulty of effective immunisation against complex parasites Lightowlers in Melbourne has developed a highly effective protein in adjuvant vaccine based on the TSOL18 antigen. Two doses of this vaccine lead to very high level protection of >98% in pigs in a variety of rural disease settings where the vaccine is most needed. However, deployment of two doses of vaccine in pigs in such settings is proving highly logistically problematic and a single dose of this vaccine has been found to be insufficiently protective. We propose here to assess for the first time the potential of a viral vectored adenovirus vaccine encoding the same TSOL18 antigen. Adenoviral vectors are known to provide excellent antibody responses with a single dose in a range of animal species, including pigs, and in humans, as illustrated by their use as a single dose vaccine in the Ebola rapid response vaccine programme in 2014. We propose to make adenoviral vectors for this Taenia antigen, test immune responses in mice initially and then critically in pigs. By comparing the immune response generated in pigs by a single dose of the new adenoviral vaccine to that generated by two doses of the existing protein in adjuvant vaccine, we will be able to determine whether a single dose adenoviral vaccine is a viable option for further development as a single dose vaccine for prevention of Taenia solium disease.
Funded Projects - Round 2
1) Rethinking ‘impossible’: creating a platform for developing novel vaccines against animal trypanosomiasis in Brazil
Professor Andrew Jackson (University of Liverpool, UK), Professor Marta M.G. Teixeira (University of Sao Paulo, Brazil), Dr. Gavin J. Wright (Wellcome Trust Sanger Institute, UK) and Professor Rosangela Zacharias (São Paulo State University, UK).
Animal African Trypanosomiasis (AAT) is a livestock disease caused by a blood parasite called Trypanosoma vivax. In South America, biting flies transmit T. vivax resulting in frequent AAT epidemics, substantial animal mortality and economic loss. This pilot project will create the capacity to develop novel vaccines for AAT. A vaccine has enormous commercial potential in Brazil, which is the world’s largest beef exporter and where meat exports are around 7% of GDP. AAT infection reduces profit per animal by 11%, so a sustainable solution to AAT will have direct economic benefits to livestock production in Brazil and across South America. However, research on human trypanosomes has shown that they change their surface proteins to prevent the immune system from identifying and destroying them. Due to this process of antigenic variation, vaccination against AAT has generally been considered impossible. However, our research on T. vivax has suggested that we can target invariant features and so remove this major bottleneck in progress. We identified a suite of T. vivax-specific cell surface proteins that do not display antigenic variation, but do elicit strong immune responses in natural infections, and we have developed a system for producing T. vivax proteins for vaccination. We will vaccinate cattle with one novel T. vivax antigen and test whether this protects them against T. vivax infection, and, if so, what kind of immune response is necessary. This will establish proof-of-principle that we can express and evaluate antigens, leading to a full-scale project testing our entire panel of T. vivax-specific proteins using different vaccination methods. This project will translate our insights into parasite biology into the first experimental vaccine, a combination of protective antigens that can be used in a clinical trial; this is an essential step in removing the burden of AAT on animal health and economic prosperity.
2) Towards edible vaccines for chickens
Dr. Kate Sutton (The Roslin Institute, UK), Professor Lonneke Verdelde (The Roslin Institute, UK), Dr. Roger New (Proxima Concepts Ltd, UK) and Professor Damer Blake (Royal Veterinary College, UK).
The burden of infectious disease in livestock continues to be a major constraint to sustained agricultural development, food security and economic benefits in developing countries. Eimeria spp. have been recognised as important parasites of poultry for more than 100 years. Risks associated with uncontrolled coccidial infection include failure of chickens to thrive, increased susceptibility to diseases, such as necrotic enteritis, compromised feed conversion and, for some species of parasite, high levels of mortality. Prophylactic anti-coccidial drugs are routinely used to control Eimeria, and live parasite vaccines are popular in some sectors of the industry although they are unsuitable for the dominant broiler sector, small holders and backyard chickens. Drug resistance and the need for in vivo propagation of live vaccines have prompted development of next generation recombinant anti-coccidial vaccines. The most important issues to tackle are (i) development of an efficacious formulation, (ii) demonstrate ease of administration with relevance to routine vaccination of chickens, independent of a cold chain and propagation in live animals, and (iii) a broad spectrum that will protect against multiple strains of Eimeria.
In this project we will test a novel vaccine caplet that can be mixed into feed making it suitable for routine administration to broilers and backyard poultry with particular relevance in low and middle income countries where poultry production is expanding rapidly. The vaccine format is highly stable in the environment and can easily be stored without a cold chain. Two promising Eimeria antigens are being taken forward in this proposal due to their ability to reduce parasite burden in infected animals when administered via injection. We will utilize an established innovative oral vaccine-delivery technology in humans and test its ability in chickens with the aim to develop a prototype vaccine against Eimeria.
3) Efficacy testing of novel immersion and oral vaccines for Aeromonas hydrophila in Tilapia and Vietnamese catfish
Dr. Thao Ngo (Biotechnology Center of Ho Chi Minh City, Vietnam), Professor Dang Thi Hoang Oanh (Can Tho University, Vietnam), Professor Alaa Eldin Eissa (Cairo University, Egypt), Professor Alexandra Adams (University of Stirling, UK), Dr. Kerry Bartie (Stirling University), Dr. Andrew Desbois (University of Stirling, UK), Professor Dirk Werling (Royal Veterinary College, UK), Dr. Callum Scott (Benchmark Animal Health Ltd.)
In 2014 the contribution of aquaculture to supply food for human consumption overtook that of wild-caught fish for the first time. Aquaculture currently contributes approximately 73.8 million tonnes of aquatic animals with a value of US$ 130 billion. This has increased by 10-12% from 59 million tonnes in 2011, representing the fastest growing animal production sector. Over 30 species are currently farmed, including tilapia and Pangasius (Vietnamese catfish also known as Tra catfish). These fish species are farmed in low and middle-income countries (LMICs) and provide an important source of revenue for many low income families supplying both the domestic and export market. Tilapia production is rapidly increasing with Egypt the third largest global producer. Tilapia and Vietnamese catfish are both produced in Vietnam. Although Vietnamese catfish production increased dramatically between 2004 and 2008, the export market has since levelled off due to public concern over disease and over use of antibiotics. Currently, disease outbreaks caused by Aeromonas hydrophila are having a major economic impact on aquaculture in both countries. No vaccine is currently available in Egypt and despite a vaccine being available for use in Vietnamese catfish, antibiotics remain the treatment of choice due to doubts over vaccine effectiveness (A. hydrophila strains are highly diverse) and the high cost of the vaccine (administered by injecting individual sedated fish). The widespread use of antibiotics within farms can encourage antimicrobial resistance, reducing the treatment options for both fish and human infection. Through a collaboration of scientists from Vietnam, Egypt and the UK we plan to test the efficacy of novel vaccines that can be easily administered (ie. immersion and oral vaccines), without the need for highly trained personnel and specialist equipment. Such vaccines are urgently needed to help prevent A. hydrophila disease outbreaks and reduce antibiotic use in both tilapia and Vietnamese catfish aquaculture.
4) New antigen identification in the African swine fever virus genome thorough a plasmid DNA library
Dr. Anna Lacasta (International Livestock Research Institute, Kenya), Professor Susan Rosser (University of Edinburgh, UK) and Dr. Fernando Rodriguez (IRTA-CReSA, Spain)
African swine fever (ASF) is a haemorrhagic devastating pig disease with mortality rates up to 100% caused by African swine fever virus (ASFV). The disease is endemic in Africa but now it is also present in the Russian Federation and other Eastern European countries, becoming a global threat. Currently, there is no vaccine nor treatment and the only countermeasures against ASF are the rapid diagnosis and culling of infected animals. However, in recent years several new approaches in the field of vaccinology have been developed against ASFV. The generation of recombinant attenuated ASFV isolates is a very promising approach, but a subunit vaccine would be a much safer and cheaper approach to vaccination and would pose less constraints for licensing in both scenarios, the European and the African. Previous studies have demonstrated the key role that humoral and cellular response can play in protection and several antigens targeting CD8+ T-cell and antibody response were identified. Unfortunately, none of them or combinations of them were able to protect a 100% of the pigs after ASFV challenge. The tested antigens eliciting an antibody response were immunodominant in the domestic pig sera, and very little is known about other possible subdominant antigens. On the other hand, an exhaustive screening of bushpig and warthog (resistant to ASF) sera was never done before. In this project we propose a comprehensive approach where we will compare the pattern of antibody recognition of domestic pig and wild pig sera using a DNA library encoding the complete ASFV Kenya 1033 genome individually and test their neutralizing capacity. The identified antigens will be susceptible to be included in a future vaccine against ASFV.