Impact case study database

Actiphage^® is an innovative new test for the rapid detection of bovine TB (bTB), Johne’s disease (JD) and other mycobacterial infections. The unique selling point of Actiphage^® is that it rapidly and precisely detects live Mycobacteria in a range of sample types including blood and milk within 6 hours. This is a significant innovation over the current rapid diagnostic Mycobacteria tests that are based on immunology (e.g. IDEXX antibody test) that do not distinguish between exposure or infection and standard PCR-based tests that do not distinguish between viable or non-viable cells. The ability to identify live cells is a unique feature of the test and also allows the test to be used to differentiate between infected and vaccinated animals. Furthermore, the test can specifically identify different species of Mycobacteria in any host including humans.

Commercialisation of Actiphage^®

In 2014, a patent application to protect the UoN technology to detect Mycobacteria using bacteriophage was filed (PCT/GB2014/052970) and a spin-out company, PBD Biotech Ltd (PBD), was established to commercialise the intellectual property under exclusive licence from the University of Nottingham (UoN). Subsequently, PBD have invested [redacted] to maintain the patent, granted in Europe (April 2019) and USA (July 2019), and to trademark the technology as Actiphage^® (2017) (a). In 2017, PBD launched Actiphage^® as a kit-based laboratory test targeted at a range of markets from research to diagnostics, with a primary focus on the detection of bTB and paratuberculosis (MAP) infections in farmed animals. The technology has been recognised by nominations for several industry innovation awards, winning: the Crop or Livestock technology at Ag-in-motion Expo (Canada, 2017); the Royal Dairy Innovation Award at Dairy-Tech (UK, 2019); the West Suffolk Award for Innovation (UK, 2019); The Cream Award (UK, 2020) and made the Cognitive top #21toWatch list (top 7 in the ‘Things’ category; UK, 2020) (b).

Between 2017 and 2020, PBD raised a total of [redacted] investment funding to commercialise Actiphage^® (a,c). To date, through the commercialisation of Actiphage^®, PBD have created 3 new jobs (PBD employees) and 5 contract positions (total 8 FTE) to support R&D and international commercial activity (a). PBD offer two laboratory test kits; Actiphage^® Rapid for detection of mycobacteria within 6 hours and Actiphage^® Core for highly sensitive and specific detection of mycobacteria within 2 days. In addition, PBD sell PCR kits for use with both Actiphage^® kits. PBD has exported test kits to over 10 countries including USA, Canada, Australia, New Zealand, Ireland, France, Korea and Italy (a). Kits have been supplied free of charge for research and validation studies, which are required for certification under World Organisation for Animal Health (OIE) standards and approval for use in bTB diagnosis in the UK and in other countries. PBD also offers a diagnostic service to detect Mycobacteria species in samples from multiple animal origins including bovine, non-bovine and exotic species. PBD Biotech’s sales to date have been [redacted] (laboratory test kits) and [redacted] (diagnostic services) (a).

Application of Actiphage^® in management of exotic species

TB is a growing problem for zoos and wildlife parks and Actiphage^® has been used to test animals including bison, deer, goats, sheep, alpaca, tapir, takin, lions, parakeets and beluga wales, offering a new way of identifying TB and informing management of protected animals (a). In 2018 Actiphage^® was used to inform decision making in an Asiatic lion conservation programme. As part of extensive ante-mortum TB testing, Actiphage^® gave positive results in the case of two lions imported from India who were in quarantine at Whipsnade Zoo (7;a,d,pg2), and in the case of a female breeding Asiatic lion based at Paignton Zoo (a). In both cases, the animals were euthanized to prevent TB being spread to other breeding lions thus protecting the UK Asiatic lion collection.

Application of Actiphage® in bTB management of cattle (UK)

All testing for bTB in the UK is done under strict government control. Testing can only be carried out using tests validated to OIE standards that have been authorised for bTB testing by Defra’s Animal and Plant Health Agency (APHA). The authorised tests are the tuberculin skin test (used for statutory bTB testing across the UK) and the interferon-gamma test (used as a supplementary test alongside the tuberculin skin test in specific TB breakdown herds). An additional OIE validated test, the IDEXX antibody test, may also be used in chronic bTB breakdowns under instruction by APHA where repeated tuberculin and interferon-gamma testing has already occurred.

The availability of Actiphage^®, and other new tests, has stimulated discussion in the media on the testing and control of bTB in the UK. The potential role of Actiphage^® in management of bTB was highlighted on BBC Radio 4 Farming Today (February 2017; November 2017; September 2018) and BBC One Six O’Clock News (December 2019) (e). Dr Rees was invited to talk about the test at the Bovine TB Symposium (March 2017), organised by the ‘Save Me Trust’ and attended by UK experts, and was subsequently invited to contribute evidence (f,g) to the review of the UK Government’s Strategy (led by Sir Charles Godfray) to eradicate bovine tuberculosis (bTB) in England (October 2018). The published review highlighted the requirement for diagnostics test, noting:

“The last few years have seen new tests proposed which are currently in the early stages of commercialisation. […] Research and development to characterise the performance of novel tests and explore new options is, we believe, of high priority” (g, pg.41, 3.50).

Development and validation of new diagnostic tests require access to materials and samples from infected farms. Such access is currently restricted by notifiable disease legislation which risks hindering bovine TB control and the development of new commercial products for the international market. Altering the legislation so that it eased the provision of research material while maintaining appropriate levels of biosecurity would be helpful (g, pg.41, 3.54).

Actiphage^® was highlighted in the review as one of the additional tests that some farmers “ would like to employ […] to accelerate the removal of infected individuals and to better manage within herd transmission” (g, pg.43, 3.40).

Following extensive lobbying by the ‘Save Me Trust’, leading UK veterinarians and other interested groups, Defra gave permission for Actiphage^® to be used within a project to eradicate bTB on a farm with a chronically infected dairy herd. Within this Gatcombe Farm (Devon) project (2017), conducted under veterinary supervision, Actiphage^® was used to detect bTB positive animals, not detected using the statutory tuberculin skin and interferon-gamma tests, and inform decisions on animal exclusion (by isolation or culling) from the herd. This formed part of a comprehensive disease management system, including stringent farm hygiene practices. The herd of 350 cows was declared Officially TB Free (OTF) in May 2018 (h) allowing the farmer to trade for the first time in seven years (e). Following successful demonstration of the potential of the test to enhance a control program at Gatcombe, APHA allowed exceptional private use of non-validated tests, including Actiphage^®, for control of bTB in cattle in England (April 2018) (i).

In 2019, PBD Biotech were invited to speak to the Welsh Government about opportunities for the use of Actiphage^® testing in Wales. In Spring 2019, the Office of the Chief Veterinary Officer for Wales granted permission for the first Welsh trial of Actiphage^®, conducted under veterinary supervision. This enabled detection of bTB in cattle considered at high risk of having bTB that had tested clear using the current government approved methods and informed decisions on herd management (animal exclusion). Acknowledging the need for new accurate bTB blood tests, the Vet supervising the Welsh trial stated “Actiphage^® is able to identify the presence of relatively low numbers of M. bovis in the blood stream of infected cattle. It is not dependent upon an immune system response to the pathogen - in contrast to current validated tests - and so has greater sensitivity than such as the official Tuberculin SICCT skin test. The benefit of using Actiphage^® is that it offers the potential for eradicating the disease from the farm; as early identification of animals at risk of bovine TB enables heightened disease management and control.” (j). Subsequent to the trial, in November 2019, the Welsh Government issued a new policy setting out terms and conditions for the exceptional use of non-validated tests, including Actiphage^®, as a supplementary approach to managing problem cattle herd breakdowns in Wales (k). Under the supplementary testing regime, APHA monitor the results and decide whether it is necessary to remove any direct contact animals from the herd under the Tuberculosis (Wales) Order 2010 (as amended) with compensation.

Summary

Actiphage^® is an innovative new test for the rapid detection of bTB, JD and other mycobacterial infections. The test has been commercialised through the formation of PBD Biotech Ltd, a UoN spin-out company. PBD Biotech Ltd has secured [redacted] to commercialise the technology, created 8 new jobs to support R&D and international commercial activity, and achieved cumulative sales of [redacted]. Actiphage^® has been approved for exceptional use in UK bTB control programs and is supporting veterinarian and farmer efforts to achieve OTF status on farms in England and Wales. In recognition of its potential to support control of mycobacterial diseases of livestock, Actiphage^® has received numerous industry awards.