Development of immunological tools for monitoring the immune response of Nile tilapia
Tilapia and other fish are increasingly important food sources, but as farming intensifies, so does disease prevalence. Developing vaccines for these diseases will require a better understanding of immune responses in tilapia. This collaboration used synthetic antibodies (sAbs) to study how these responses work.
Outcome: The team was successful in producing sAbs to bind one of their cell marker targets, which they used in a challenge study, and made good progress in identifying several other candidates. Work on refining and optimising these sAbs is continuing.
Scientists: Dr Kim Thompson, Professor Sachdev Sidhu, Professor Alexandra Adams, Dr Alasdair Nisbet, Dr Hoang Nguyen, Dr Nguyen Ngoc Phuoc, Professor Ruth Zadoks.
A single dose vectored Taenia solium vaccine
The tapeworm T. solium, a cause of seizures in humans, uses pigs as an intermediate host. The two vaccine doses required for protection in pigs is logistically problematic in rural settings. This project tested the use of an adenoviral vector, which can protect against other diseases after a single dose, to deliver the T. solium antigen to pigs.
Outcome: Antibody titres in pigs vaccinated using the adenoviral vector were lower than the levels required for protection. This project showed therefore that this is not a suitable way to immunise pigs against T. solium.
Scientists: Professor Adrian Hill, Professor Marshall Lightowlers, Professor Bryan Charleston.
Low-cost thermostabilisation of a Rift Valley fever vaccine for veterinary use
A common barrier to vaccine deployment in rural settings is the need for refrigeration. This project tested methods of thermostabilising a Rift Valley fever vaccine and evaluated the vaccine’s viability after prolonged periods at low, medium and high temperatures.
Outcome: A stabilised liquid vaccine formulation could withstand short periods outside a cold chain, while a freeze-dried vaccine was viable even after six months at 30°C, which will greatly facilitate use and distribution in LMICs.
Scientists: Professor George Warimwe, Dr Alexander Douglas, Dr Michael Francis.
Rethinking ‘impossible’: creating a platform for developing novel vaccines against animal trypanosomiasis in Brazil
The blood parasite Trypanosoma vivax causes substantial mortality and economic loss in Brazil’s beef cattle sector. Related human trypanosomes are known for their antigenic variability, thought to make vaccination elusive – but research on T. vivax has identified invariant antigens. This project was set up to test the efficacy of these antigens as vaccine candidates.
Outcome: The proteins tested were shown to be immunogenic in mice and goats, but this antigenicity was not sufficient to confer immunity. Therefore, these proteins are not yet proven to be robustly protective against T. vivax.
Scientists: Professor Andrew Jackson, Professor Marta Teixeira, Dr Gavin Wright, Professor Rosangela Zacarias Machado.
Towards edible vaccines for chickens
Drug resistance and vaccine limitations have prompted development of recombinant vaccines against the important poultry parasite Eimeria. This project tested the use of an innovative oil formulation for delivering antigens to chickens orally. Mixing this formulation into feed could enable routine Eimeria vaccination in the broiler and backyard sectors.
Outcome: The formulation was able to bind to chicken intestinal epithelial cells and induce both a systemic and mucosal immune response, serving as an important proof-of-concept for this technology.
Scientists: Dr Kate Sutton, Professor Lonneke Vervelde, Dr Roger New and Professor Damer Blake.
Efficacy testing of novel immersion and oral vaccines for Aeromonas hydrophila in tilapia and Vietnamese catfish
Aeromonas hydrophila is a major cause of aquaculture disease especially on fish farms in low- and middle-income countries, harming the livelihoods of many low-income families. The only vaccine available for Vietnam’s catfish farmers is hard to administer and has uncertain efficacy; no vaccine is available for tilapia farmers in Egypt. This collaboration tested novel vaccine candidates delivered orally and through immersion.
Outcome: The team developed and tested an inactivated vaccine by oral, immersion and injection routes. A challenge study showed good survival in fish primed by immersion and boosted by injection. Boosting with immersion also showed promising signs worth repeating with more replicates.
Scientists: Dr Thao Ngo, Professor Dang Thi Hoang Oanh, Professor Alaa Eldin Eissa, Professor Alexandra Adams, Dr Kerry Bartie, Dr Andrew Desbois, Professor Dirk Werling, Dr Callum Scott.
New antigen identification in the African swine fever virus genome thorough a plasmid DNA library
African swine fever causes high mortality in pigs and is becoming a global threat, with no vaccine available. Recombinant attenuated isolates show promise, but a subunit vaccine would be safer and cheaper. This project used a plasmid library to identify antigens for future vaccine use.
Outcome: Screening assays allowed the selection of seven antigens for further investigation; the next stages will test these antigens’ immunogenicity.
Scientists: Dr Anna Lacasta, Dr Fernando Rodríguez, Dr James Johnson.
Construction of foot-and-mouth disease (FMD) virus-specific phage-display libraries and epitope identification for improved FMD vaccines generation
Foot-and-mouth disease is one of the most economically important livestock diseases and is endemic in large parts of Africa, Asia and South America. The virus has a high mutation rate, causing antigenic variation between strains and affecting vaccine efficacy. This project seeks to identify antigenic determinants within the viral capsid in strains from different parts of the world. This will help in identifying critical epitopes, which can be implemented to produce improved vaccines.
Outcome: This project is ongoing.
Scientists: Dr Pamela Opperman, Dr Melanie Chitray, Dr Francois Maree, Dr Alejandra Capozzo, Dr Mariano Perez-Filgueira, Dr Anna Ludi, Dr Richard Reeve.
Isolation and purification of Nairobi sheep disease virus for development of a thermostable vaccine
The tick-transmitted Nairobi sheep disease virus causes severe illness in sheep and goats, with fatalities reaching up to 90% in affected animals. The disease causes considerable losses, especially to small scale farmers in Eastern and Central Africa. This project aimed to generate and test an inactivated vaccine candidate using virus isolates collected from ticks.
Outcome: The team collected ticks from three sites and inactivated a vaccine candidate for use in vaccination. They tested this candidate in sheep, and showed that a double dose has protective potential.
Scientists: Dr Caroline Wasonga, Dr Joel Lutomiah, Dr Jennifer Duncan, Dr Michael Muthamia Kiraithe, Dr Allan Ole Kwallah, Edna M Ondari.
Immunisation of tilapia broodstock as a strategy to prevent vertical transmission of tilapia lake virus
With tilapia fry traded for aquaculture, there is a risk of disease spreading worldwide. Immunising fry would help control and prevent this spread. Protective maternal antibody transfer to offspring has been confirmed in several fin fish species, but little is known about this in tilapia. Vaccinating broodstock against the rapidly spreading tilapia lake virus may help prevent vertical transmission – this project sought to test this.
Outcome: The project led to the development of two inactivated vaccines conferring significant protection in juvenile tilapia. Antibodies were detected in 1-3 day old larvae of vaccinated broodstock, but not in 7 day old larvae, suggesting a short persistence of maternal immunity.
Scientists: Dr Pattanapon Kayansamruaj, Dr Ha Thanh Dong, Dr Channarong Rodkhum, Dr Saengchan Senapin, Dr Jorge del-Pozo, Dr Janina Z Costa, Dr Kim Thompson.
Identification of virulence factors as novel vaccine targets for contagious bovine pleuropneumonia by whole genome saturated mutagenesis
Improved vaccines against contagious bovine pleuropneumonia are urgently needed, but this will require deeper insights into host-bacteria interactions. This project sought to generate a mutant library to identify bacterial genes involved in misleading of the host’s immune response.
Outcome: A library of 800 mutants was successfully generated, with more planned, and a host cell cytotoxicity assay has been established.
Scientists: Dr Elise Schieck, Dr Musa Hassan, Dr Robert Kammerer.
Discovery of T cell epitopes of the intracellular parasite Babesia bovis using immunoproteomic and immunoinformatic strategies
The tick-transmitted parasite Babesia bovis causes babesiosis in tropical and subtropical regions, causing high mortality in infected cattle. Current live vaccines are effective but carry significant drawbacks, and there is an urgent need for new vaccines. This work aims to identify key protein fragments involved in the bovine immune response against B. bovis using mass spectrometry, advanced immunoinformatics and machine-learning.
Outcome: This project is ongoing.
Scientists: Dr Silvina Wilkowsky, Dr Nicola Ternette, Magali Valenzano, Professor Morten Nielsen.
Immunogenicity study of matrix 2 ectodomain proteins displayed on nodavirus-like particles as a universal avian influenza virus vaccine for chickens
Avian influenza causes severe outbreaks leading to economic and wildlife losses and potential human health risks. A vaccine targeting all strains is urgently required. A candidate has shown promising efficacy against human influenza A virus in mice. This work tests whether the candidate may confer universal protection against avian influenza in chickens.
Outcome: The virus-like particles constructed were shown to be antigenic, inducing a humoral response against the avian influenza virus in vivo.
Scientists: Dr Mariatulqabtiah Abdul Razak, Professor Wen Siang Tan, Dr Kok Lian Ho, Professor Abdul Rahman Omar, Professor Munir Iqbal.