Corporate report

Number of animals used: 2022

Updated 12 July 2023

The following tables provide the numbers of animals used, per species, at our scientific campuses at Porton (including Porton Biopharma Limited (PBL)), Colindale and Chilton, in 2022.

Site	Mice	Hamsters	Guinea pigs	Rats	Rabbits	Ferrets	Turkeys	Non-human primates (NHPs)
Porton	493	443	226	12	0	97	0	54
PBL	0	0	752	0	12	0	0	0
Chilton	926	0	0	9	0	0	0	0
Colindale	12	0	57	0	0	4	12	0

Porton

All animals were used for the development and testing of vaccines or therapies to counteract infectious diseases that cause a direct threat to human health worldwide.

Research activities in 2022 included the development of drugs and vaccines against a wide range of potential viral and bacterial threats. The maintenance and further refinement of this capability has enabled us to continue studies on the variants of COVID-19.

This has provided a rare capability to international funders such as CEPI and gives assurance to the public and government that when a new infectious disease threat emerges, the UK Health Security Agency (UKHSA) is well-rehearsed in assisting in the development of new countermeasures to protect the population.

Of the non-human primates used, 50 experienced only mild or non-recovery procedures with 4 classified as moderate. For other species, 53% underwent procedures that were classified as mild, 16% as moderate and 31% as severe.

Tuberculosis

Guinea pig and mouse studies

Drug-resistant tuberculosis (TB) is a growing threat to human health and continues to be one of the most urgent and difficult challenges facing global TB control. Patients who are infected with strains resistant to isoniazid and rifampicin, called multidrug-resistant (MDR) TB, are practically incurable by standard first-line treatment. The TB research community is working collaboratively to ensure that TB does not once again become an incurable disease. UKHSA is working with TB drug developers, within the global research community, by evaluating the efficacy of new and novel drug compounds in our optimised in vivo models, to ensure that the most safe and promising drug candidates progress through to clinical trials in humans.

Publications

Evangelopoulos D, Shoen CM, Honeyborne I, Clark S, Williams A, Mukamolova GV, Cynamon MH, McHugh TD. ‘Culture-Free Enumeration of Mycobacterium tuberculosis in Mouse Tissues Using the Molecular Bacterial Load Assay for Preclinical Drug Development’. Microorganisms. 2022 Feb 17;10(2):460.

Macaque studies

Work has been performed to support the global effort to combat tuberculosis. Studies using the non-human primate (macaque) models of Mycobacterium tuberculosis (M. tuberculosis) infection have supported the clinical development of new TB vaccine candidates and new TB drugs and provided data to inform their further development for clinical deployment. To assist efforts to identify biomarkers of disease progression and correlates of risk and protection that could revolutionise the development of new interventions, detailed immune profiling of responses induced by vaccination, treatment and Mycobacterium tuberculosis infection has been conducted. The potential roles of immune responses induced following vaccination with Bacillus Calmette-Guérin (BCG) vaccine in protection from M. tuberculosis infection or cancer have been explored.

Publications

Laura Sibley , Andrew White, Charlotte Sarfas, Jennie Gullick, Fergus Gleeson, Faye Lanni, Simon Clark, Emma Rayner, Santiago Ferrer-Bazaga, Fatima Ortega-Muro, Laura Alameda, Marisa Martinez, Inigo Angulo-Barturen, Aldolfo Garcia, Juan J. Vaquero, Henry E. Pertinez, Geraint Davies, Mike Dennis, Ann Williams, Sally Sharpe. ‘Determination of the Pharmacokinetics and Pharmacodynamics of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in a cross-over cynomolgus macaque model of Mycobacterium tuberculosis infection’. Pharmaceutics 2022, 14(12), 2666.

Isabel Nogueira, Martí Català, Andrew D White, Sally A Sharpe, Jordi Bechini, Clara Prats, Cristina Vilaplana, Pere-Joan Cardona. ‘Surveillance of daughter micronodule formation is a key factor for vaccine evaluation using experimental infection models of tuberculosis in macaques’. Pathogens 2023,12(2), 236.

Fenn, Joe; Ridgley, Laura; White, Andrew; Sarfas, Charlotte; Dennis, Mike; Dalgleish, Angus; Reljic, Rajko; Sharpe, Sally; Bodman-Smith, Mark. ‘Bacillus Calmette-Guerin (BCG) induces superior anti-tumour responses by Vδ2+ T-cells compared to the aminobisphosphonate drug zoledronic acid’. Clinical and Experimental Immunology 2022 Jun 23;208(3):301-315.

Paula Ruibal, Kees L. M. C. Franken, Krista E. van Meijgaarden, Marjolein van Wolfswinkel, Ian Derksen, Ferenc A Scheeren, Charlotte Sarfas, Sally A. Sharpe, Andrew D. White, Thomas Abeel, Tom H. M. Ottenhoff and Simone A. Joosten. ‘Identification of novel HLA-E-binding Mtb-derived epitopes through improved prediction models’. Journal of Immunology September 12, 2022, ji2200122.

Laura Hunter, Suzie Hingley-Wilson, Graham Stewart, Sally Sharpe and Francisco Javier Salguero. ‘Dynamics of macrophage, T and B cell infiltration within pulmonary granulomas induced by Mycobacterium tuberculosis in two non-human primate models of aerosol infection’. Frontiers in Immunology 2022 Jan 6;12:776913.

C. difficile

UKHSA’s work on identifying therapies and treatments to protect the public from the disease caused by C. difficile continued in 2022 with assessments of possible vaccines in a model of infection.

SARS-CoV-2

Small rodent aerosol non-lethal disease models were used to assess the efficacy of a range of candidate clinical prophylactics and treatments for COVID-19 disease. This model was also used to assess the risk of increased disease, newly emerging variants of concern and the potential for immune escape from immunity elicited by vaccines and prior exposure to earlier circulating variants of concern (convalescence). The model has been subject to additional development to allow a deeper understanding of the contributions different elements of the immune system make to vaccine protection, as well as the assessment of vaccines that provide broader protection against SARS-CoV-2 variants. The ferret model of SARS-CoV-2 and influenza has been used to confirm the safe delivery of the live attenuated influenza vaccine (LAIV) when administered in the context of an ongoing COVID-19 infection. The team has published the findings of this work extensively in the peer-reviewed literature, as well as presented orally to the international community such as at events sponsored by the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC).

Publications

Findlay-Wilson S, and others. ‘Development of a cost-effective ovine antibody-based therapy against SARS-CoV-2 infection and contribution of antibodies specific to the spike subunit proteins (2022)

Ryan KA and others. ‘Sequential Delivery of Live Attenuated Influenza Vaccine and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the Ferret Model Can Reduce SARS-CoV-2 Shedding and Does Not Result in Enhanced Lung Pathology’ (2022)

Ryan KA and others. ‘Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant’ (2023)

Handley A, and others. ‘SARS-CoV-2 Disease Severity in the Golden Syrian Hamster Model of Infection Is Related to the Volume of Intranasal Inoculum’ (2023)

Davies, E.R. and others. ‘The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection’

Influenza

UKHSA is appointed as an Outside Testing Laboratory for AstraZeneca which conducts vaccine release testing. In brief, the ferret non-lethal disease model of influenza has been used to GMP safety test the live attenuated influenza vaccine (LAIV) produced by Astra Zeneca. LAIV has been used in the UK since 2013 to protect children against infection with influenza. The vaccine is the preferred product for children in flu ‘at-risk’ groups aged from 2 to 17 years (inclusive) and is used as part of the Department of Health and Social Care’s routine children’s vaccine programme delivered in schools and general practices. The licence has also been used for supporting activities around the rollout of LAIV, including the qualification of a diversified ferret colony and screening of potential vaccine strains.

The development of a small rodent non-lethal disease model for influenza was undertaken to assess the pathogenicity of a range of seasonal and avian influenzas that have the potential to cause human infection. This model has been compared successfully to the gold-standard ferret model when characterising virus infection, and going forward will be evaluated for its utility in assessing countermeasures against influenza.

Publications

Paterson, J. and others. ‘Infection with Seasonal H1N1 Influenza Results in Comparable Disease Kinetics and Host Immune Responses in Ferrets and Golden Syrian Hamsters’.

Bacterial pathogens

The plague, caused by Yersinia pestis, is estimated to have been responsible for a least 200 million deaths throughout recorded human history. Pneumonic plague is of particular concern to human health, as positive outcomes rely on antibiotic treatment being administered early. Mice have been used as an effective disease model to assess the efficacy of medical interventions to aerosolised Yersinia pestis. Work performed under this project has contributed to the justification of further research into potential vaccine candidates.

Burkholderia pseudomallei is the causative agent of melioidosis. Infection with this bacterium is inherently resistant to many antibiotics and treatment is often ineffective. Mice have been used as an effective disease model to assess both prophylactic and therapeutic countermeasures. In addition, work carried out on these projects have contributed to the body of knowledge on the effective use of medical interventions to Burkholderia pseudomallei and provides justification into further research into these candidates.

Emerging and re-emerging viral pathogens

In 2022, work was carried out on multiple pathogens, including those categorised as hazard group 4. Studies included developing a hamster model of Nipah virus disease, which involved the determination of an appropriate challenge route and dose. This model was subsequently used to assess vaccine candidates. Similarly, the mouse model of Crimean-Congo haemorrhagic fever (CCHF) virus was employed to assess the vaccine efficacy of several vaccine candidates across different platforms, including viral vectors, recombinant protein and mRNA vaccines. Work on assessing the protective effects of RNA-based vaccine candidates was also undertaken with other viral haemorrhagic fevers: Lassa, Ebola and Marburg viruses. In addition, the protective titre of convalescent antibody preparations was assessed in CCHF, Lassa, Rift Valley fever and Chikungunya virus models, allowing the identification of parameters indicating vaccine efficacy without the requirement for challenge studies, thus potentially contributing to future reductions in animal numbers for studies with infectious virus. Rats were used to assess their susceptibility to mpox (monkeypox) in response to a recent outbreak in the context of addressing the zoonotic potential of viral transmission.

Publications

Saunders JE, Gilbride C, Dowall S, Morris S, Ulaszewska M, Spencer AJ, Rayner E, Graham VA, Kennedy E, Thomas K, Hewson R, Gilbert SC, Belij-Rammerstorfer S, Lambe T. ‘Adenoviral vectored vaccination protects against Crimean-Congo haemorrhagic fever disease in a lethal challenge model’. EBioMedicine. 2023 Apr;90:104523. doi: 10.1016/j.ebiom.2023.104523.

Development of in vitro methods

In 2022, 9 macaques were used under non-recovery procedures to provide tissues for the development of organ-on-a-chip culture methods that will replace and reduce animal use, and to provide data on the influence of the gut microbiome on disease progression and on vaccine efficacy.

Porton Biopharma Limited (PBL)

PBL’s work is focussed on the quality-assured development of life-saving biopharmaceuticals. We manufacture the licensed product Erwinase, a childhood leukaemia therapy, and the UK’s licensed anthrax vaccine.

As part of the licence, there is a requirement to undertake a limited number of animal tests to ensure that each batch of the vaccine is safe and effective. This involves guinea pigs and rabbits. Work is ongoing to replace the work in guinea pigs where some animals are likely to experience severe severity, with tests of mild severity using fewer animals.

Chilton

During 2022, UKHSA Chilton used a total of 935 animals in the projects detailed below. The majority of these animals suffered no or mild harm, with some suffering moderate harm.

Radiation-induced leukaemogenesis

A total of 174 mice were used for the breeding and maintenance of 2 genetically modified mouse models used to better understand how radiation can lead to the development of leukaemia. No other procedures were carried out and the majority of the mice were returned as sub-threshold with around 10% mild threshold. Due to the end of 2 PhD projects, it was no longer a requirement to maintain these colonies, and they are now stored as frozen stocks at the MRC Harwell.

Radiation-induced intestinal carcinogenesis

In total, 596 mice were bred and used in continued experimental studies where they were exposed to one or two doses of X-rays at different ages (2, 10, 30, 45 or 90 days). The number of intestinal tumours that result from these different doses will be counted and compared to provide information on what effect splitting radiation doses has on radiation-induced tumour numbers.

Metabolic effects of sunlight

A total of 65 mice were used to assess the potential benefits of low-level, non-burning ultraviolet A light (equivalent to UK sunlight), specifically reducing the risk of metabolic disease. Mice were given a high-fat diet to accrue low-level lipid retention within organs, altering metabolic state without adverse pathology. Ultraviolet A light at non-burning doses was then used on a subset of mice to examine any systemic effect on organs through the use of these wavelengths. Mice gained weight compared to the baseline control group (retained on a low-fat diet) but suffered no adverse effects (reaching no more than a mild threshold). After the harvest of organs at 20 weeks of age, the results of this pilot study demonstrated that UVA light treatment reduced lipid droplet size within the liver. This will be taken forward into a bigger trial, where the result will be confirmed in a larger cohort, and assessed to explore if it reduces the likelihood of liver scarring (cirrhosis) and iron retention that occur at later stages of liver disease.

Biological effects of electromagnetic fields

A study used 23 mice that underwent non-invasive observation and assessment in specialised cages, which allowed assessment of behavioural circadian rhythms (24-hour biological rhythms), sleep and home cage behaviour using video tracking. They then underwent tests to examine their exploratory and anxiety responses to unfamiliar surroundings. These studies were carried out in normal and constant lighting conditions to mimic that experienced by shift workers. Tissues from the mice were used for molecular, gene and metabolite analysis to understand the observed changes in behaviour.

Toxicity of inhaled environmental particles

In a set of experimental studies, 9 rats and 68 mice were used to investigate how different types of air pollution particles (such as diesel exhaust and dust mites) impact the lung and how they may interact with each other resulting in lung disease. Air pollution, both indoors and outdoors, is a complex mixture comprising gases and different particle types that when inhaled can adversely affect human health, in particular the lung, and conditions such as asthma. The level of severity experienced by these animals was within the mild (22%) to moderate (78%) categories, predominantly resulting from nasal and lung instillation procedures and resulting in airway inflammation and sensitivity that ensues. Note that previous work on this licence investigating the inhalation of radioactive steel particles (formed during the decommissioning of nuclear facilities) was published this year.

Colindale

Guinea pigs

The year 2022 saw the use of 57 guinea pigs. In flu H3 subtype assays, we use guinea pig red blood cells and in serology studies, we use their red blood cells to determine the level of immune response in humans. The actual severity was classified as non-recovery.

Mice

In total, 12 mice were used in 5 tests to detect bacterial toxins (clostridium botulinum and clostridium tetani).  These tests are performed using clinical samples obtained from patients suspected of having contracted the bacteria. For most mice, these regulated procedures were classified as mild, but 2 of the tests were positive, that is showing signs of botulinum clostridium in the patients’ clinical sample and so these mice were classified as having experienced severe severity.

Turkeys

To conduct influenza assays, 12 turkeys were used to supply normal red blood cells. The actual severity was classified as mild.

Ferrets

In total, 4 ferrets were used to produce antisera against new and emerging influenza strains, contributing to the development of flu vaccines in the UK. The actual severity was classified as mild.