Bovine Mastitis Control by Local Administration of Polyplex Nanoparticles

Lead Research Organisation: Royal Veterinary College
Department Name: Pathology and Pathogen Biology

Abstract

There are millions of cases of mastitis annually. Mastitis can linger, and often recurrent signs often follow acute infection. Rates of antibiotic-resistant Staphylococcus aureus are high in mastitis isolates from Brazil. The situation calls for better control, including hygiene practices that kill "protected" pathogens, where protection is conferred by antimicrobial resistance and by the ability of common mastitis pathogens to "hide" from antimicrobials within biofilms and host cells. These challenges inspired us to test the potential use of a micro-biocidal polymer to kill antimicrobial resistant, biofilm and intracellular forms of S. aureus. Our preliminary (in vitro) results are promising and have prompted this research proposal, which aims to develop a novel anti-mastitis technology for practical applications on the Brazilian and global dairy farms. In this project, we will test the effectiveness of the approach as a teat disinfectant on teat samples obtained from abattoirs. We are hopeful that the results will help to guide us towards the development of an improved teat-dip control for mastitis, and in the longer term an improved therapy.

Planned Impact

CAREER DEVELOPMENT THROUGH TRAINING - WHO?: Students, young researchers and scientific staff will gain training. HOW? The project will train young researchers in both the UK and Brazil. These researchers will be trained in state of the art methods for AMR, drug development and biopharmaceuticals delivery. The work will involve both research and development including discussion with regulatory agencies. Therefore, the project leaders will gain broad exposure to a range of methods that are widely relevant to disease control in practice. Also, the experience is highly relevant to industry in both countries. Finally, researchers with an understanding of the challenges of mastitis control and modern strategies to tackle the problem are of value to the government and in forming new policy. The TIME FRAME for impact will be the span of the project lifetime, and job satisfaction, skills development an on-ward employment will be monitored to MEASURE impact.

WIDER EDUCATION THROUGH COMMUNICATIONS AND ENGAGEMENT - WHO?: Farmers and the public will gain knowledge. HOW? Engagement with scientists: A key object of the project is to publish the work in high quality and accessible scientific journals, with raw data and full methods descriptions available. This will help to ensure maximum method and technology uptake. The TIME FRAME for impact will be the final months of the project, and presentations and publications will be used to MEASURE impact. Engagement with private sectors: In the UK, the RVC and SoP have extensive links with companies that develop therapies for animal and human health. In Brazil, MVdS interacts with most or all of the important animal health companies. The TIME FRAME for impact will be the final months of the project lifetime, and engagement with industry will be used to MEASURE impact. Engagement with dairy farmers: The RVC and USP maintain active cooperation with national dairy associations and individual farmers in Brazil. FThe TIME FRAME for impact will be the span of the project, and engagement with farmers will be used to MEASURE impact.
ECONOMIC DEVELOPMENT THROUGH COMMERCIAL EXPLOITATION - WHO?: Industry and farmers will be able to exploit the project results. HOW?: We have already taken steps to ensure that parts of the base technology are protected with patent applications, and we have made progress in out-licensing the technology. Indeed, the technology currently underpins two Phase I/II PoC trials in humans. This general pathway will be pursued further to ensure maximal exploitation of the project outcome. In addition to mastitis, we see several exploitation opportunities and we will pursue the most appropriate routes selectively. The TIME FRAME for impact will be the final months of the project lifetime, and investment from industry will be used to MEASURE impact.

FOOD SECURITY AND ANIMAL WELFARE IMPROVEMENTS - WHO? People and animals will enjoy improved lives in the developed and developed countries. HOW? Infection control will improve the production and safety of food systems and the quality of life of animals and staff involved in the dairy industries in developed and developing countries. The development interests of UK and Brazil are very well aligned in this project. In both countries health in the dairy industry is a major concern within food security and safety. The project aligns with the government's UK Strategy for Agricultural Technologies and DfID priorities. The project will increase the pace and scale of uptake of an agricultural innovation by farmers in an important developing country - Brazil. Small producers will benefit from a more reliable and efficient production, which will improve financing and ability to plan. The outcome will help control mastitis that has a large burden within the animal and human health and farm economics.

Publications

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Description - What were the most significant achievements from the award?
We developed novel antimicrobial nanoparticles that show promise as formulations to control mastitis in dairy cattle. The formulations show strong tissue adherence properties, potent antibacterial effects against biofilm and intracellular forms of mastitis pathogens. Also, we characterised the biofilm and host cell invasive properties of S. aureus strains isolated from mastitis cases in Brasil, providing insight into the nature of the disease in the region.

- To what extent were the award objectives met? If you can, briefly explain why any key objectives were not met.
All project objectives, as proposed were met.

- How might the findings be taken forward and by whom?
We aim to take the outcome forward within a field trial on dairy farms in Brasil. Pending funding we will do this with our existing Brasilian partners. Also, we have opportunities to engage with animal health companies interested in the area.
Exploitation Route The goal is to provide an improved teat dip and udder installation. These products would be further developed by others and partners could take the techology to market. Also, the work has been picked up by other laboratories, which are devleoping related strategies which could progress in a similar way.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description We have used some of our data to support discussions with a global animal health company, which has led to licencing terms discussions.
First Year Of Impact 2018
Sector Agriculture, Food and Drink
Impact Types Economic

 
Company Name Tecrea Ltd 
Description Founded in 2012, as a spinout from the Royal Veterinary College, University of London, Tecrea have already developed a line of tools that improve scientific experiments through enhanced delivery of a range of molecules into cells. Also, Tecrea's technology has been licensed-out to several biotechs who have progressed to Phase I/II clinical studies. 
Year Established 2012 
Impact The company licenses underpinning technology from Prof Good's laboratory and the project has informed opportunities for investment and following on support.
Website http://www.tecrea.co.uk
 
Description Discussion with 3 animal health companies 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Third sector organisations
Results and Impact We discussed our project objectives, results and next steps along with regulatory and development needs and opportunities.
Year(s) Of Engagement Activity 2018,2019