Corporate report

Number of animals used: 2023

Updated 11 September 2024

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 2023.

Porton

Table 1. Numbers of animals used, per species, at Porton

Severity	Mice	Guinea pigs	Hamsters	Ferrets	Rats	Cotton rats	Rabbits	Turkeys	Non-human primates (NHPs)
Non- recovery	0	0	0	0	0	0	0	0	3
Mild	261	143	197	81	14	28	0	0	23
Moderate	82	5	132	37	0	18	0	0	7
Severe	31	0	20	18	0	0	0	0	0
Total	374	148	349	136	14	46	0	0	33

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 world-wide. Research activities in 2023 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 coronavirus disease 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 UKHSA is well rehearsed in assisting in the development of new countermeasures to protect the population. 

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 are working collaboratively to ensure that TB does not once again become an incurable disease. UKHSA are 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.

References

Larenas-Muñoz F and others. ‘Characterisation and development of histopathological lesions in a guinea pig model of Mycobacterium tuberculosis infection’ Frontiers in Veterinary Science 2023: volume 10, page 1,264,200

Macaque studies

Work has been performed to support the global effort to combat tuberculosis.

Studies using the nonhuman 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 revolutionize the development of new interventions, detailed immune profiling of responses induced by vaccination, treatment and M. tuberculosis infection have 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.

References

Morrison AL and others. IV BCG vaccination and aerosol BCG revaccination induce mycobacteria-responsive γδ T cells associated with protective efficacy against M. tb challenge Vaccines 2023: volume 11, issue 10, page 1,604

White AD and others. Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates Frontiers in Immunology 2023, Sec. Vaccines and Molecular Therapeutics: volume 14, page 1,246,826

Ruibal P and others.  Identification of HLA-E Binding Mycobacterium tuberculosis-Derived Epitopes through Improved Prediction Models. Journal of Immunology 2022: volume 209, issue 8, pages 1,555-1,565

Peralta Alvarez MP and others. ‘Low-dose M.tb infection but not BCG or MTBVAC vaccination enhances heterologous antibody titres in non-human primates’ Frontiers in Immunology 2024: volume 15, page 1,387,454

SARS CoV-2

Small rodent 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 the live attenuated influenza vaccine (LAIV) when administered in the context of an ongoing COVID-19 infection. The team have published the findings of this work extensively in the peer reviewed literature as well as presented orally to the international community such as WHO and ECDC-sponsored events.

References

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 Antiviral Research 2022: volume 203, page 105,332

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 Journal of Infectious Diseases 2022: volume 225, issue 3, pages 404-412

Ryan KA and others. Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant Public Library of Science Pathogens 2023: volume 19, issue 4, e1011293

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 Viruses 2023: volume 15, issue 3, page 748

Davies ER 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 Viruses 2023: volume 15, issue 5, page 1,133

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 safety test the 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.  

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 the utility in assessing countermeasures against influenza.   

References

Paterson J and others. Infection with Seasonal H1N1 Influenza Results in Comparable Disease Kinetics and Host Immune Responses in Ferrets and Golden Syrian Hamsters Pathogens 2023: volume 12, issue 5, page 668 

Gijs Hardenberg and others. Polymeric nanoparticle-based mRNA vaccine is protective against influenza virus infection in ferrets Molecular Therapy Nucleic Acids 2024: volume 35, issue 1, page 102,159

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 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

Studies during 2023 focussed on developing models of disease and intervention testing for high consequence infectious disease pathogens, specifically Hantavirus, Crimean-Congo Haemorrhagic Fever virus, Lassa virus and Nipah virus. Studies included assessing the effectiveness of viral-vectored vaccine candidates, polyclonal antibody therapies and convalescent human sera for their ability to protect against live virus challenge. The Nipah virus disease model established in 2022 has been used to study the pathogenicity of disease progression and screen vaccine candidates, demonstrating promising results.

References

Findlay-Wilson S Establishment of a Nipah Virus Disease Model in Hamsters, including a Comparison of Intranasal and Intraperitoneal Routes of Challenge Pathogens 2023: volume 12, issue 8, page 976

Graham VA and others. Pathogenesis of Rift Valley Fever Virus in a BALB/c Mouse Model Is Affected by Virus Culture Conditions and Sex of the Animals Viruses 2023: volume 15, issue 12, page 2,369

Jack E Saunders and others. ‘Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model’ eBioMedicine 2023, volume 90, page 104,523

Development of in vitro methods

In 2023, 3 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)

Table 2. Numbers of animals used, per species, at PBL

Severity	Mice	Guinea pigs	Hamsters	Ferrets	Rats	Cotton rats	Rabbits	Turkeys	NHPs
Mild	0	0	0	0	0	0	12	0	0
Moderate	0	273	0	0	0	0	0	0	0
Severe	0	495	0	0	0	0	0	0	0
Total	0	768	0	0	0	0	12	0	0

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

Table 3. Numbers of animals used, per species, at Chilton

Severity	Mice	Guinea pigs	Hamsters	Ferrets	Rats	Cotton rats	Rabbits	Turkeys	NHPs
Mild	291	0	0	0	27	0	0	0
Moderate	279	0	0	0	0	0	0	0
Severe	2	0	0	0	0	0	0	0
Total	572	0	0	0	27	0	0	0

During 2023, UKHSA Chilton used a total of 572 animals (27 rats and 545 mice) in the projects detailed below. The majority of these animals suffered no or mild harm (291, 50.8%), with 279 (48.8%) suffering moderate and 2 (0.3%) suffering severe harm.

Radiation-induced intestinal carcinogenesis

Animal studies are crucial to support those monitoring humans exposed to radiation to continually improve the scientific understanding that underpins effective radiation protection. Current uncertainties include the risks posed by low doses of radiation, and whether age, genetic factors and/or underlying disorders increase susceptibility to radiation-induced diseases.

In total, 480 mice were used to investigate the effects of age and human-relevant genetic mutations increasing colon tumour formation on the susceptibility to radiation-induced colon cancer. The complex processes by which radiation leads to cancer development cannot currently be fully modelled in non-animal systems, with mouse models providing essential human-relevant data.

The majority of these mice suffered mild or no harm (268, 55.8%), with 210 (43.8%) suffering moderate and 2 (0.4%) severe harm. The mild and moderate harms were predominantly due to colon tumours development and include lack of appetite, weight loss, rectal bleeding or prolapse. Some female mice (less than 5%) of the strain used can also develop mammary tumours in older age (not related to radiation). Thus, all mice were closely monitored for signs of disease and weighed frequently, and any animals were humanely killed before their experimental time point if they lost 20% of their body weight, demonstrated blood loss that did not resolve within 48 hours, developed a rectal prolapse that did not resolve within 12 hours or a mammary tumour, or showed signs of poor health (a body conditioning score less than 2). Of the 2 mice suffering severe harms, one mouse died following an unexpected seizure and another was found dead with no previous observed welfare concerns. Since it was impossible to confirm whether or not the deaths were due to the procedures, both animals were assigned a severe classification.

The results achieved will further contribute to the evidence base used by international organisations (for example, International Commission on Radiological Protection (ICRP), International Atomic Energy Authority (IAEA)), relevant government agencies (for example, Department of Health), and the nuclear industry to refine models for cancer risk estimation in human populations and improve radiation protection advice and guidance.

Toxicity of inhaled environmental particles

Air pollution, both indoors and outdoors, is a complex mixture comprising gases, chemicals, and particles of different types, that when inhaled adversely affect human health, in particular the lung and conditions such as asthma. While associations between air pollution and poorer respiratory health are well-established, the biological processes linking individual and mixtures of pollutants with specific health outcomes requires further investigation to improve interventions and public health strategies.

In total, 27 rats and 65 mice were used in a set of experimental studies to investigate how such pollution exposures (NO2 gas, indoor dust, diesel particles, and dust mite allergens) may interact with each other to cause lung disease beyond what was previously understood from examining these pollutants alone. The complex responses of normal and asthmatic airways cannot currently be fully modelled in non-animal systems, with rodent models providing essential human-relevant data.

The level of severity experienced by these animals was within the mild-moderate range (23, 25% mild; 69, 75% moderate), predominantly resulting from lung inhalation and instillation procedures and the resulting lung disease that ensued. These included mild disorientation after general analgesia, stress due to being restrained within an exposure tube and sneezing as a natural reaction to dosing within the nose, with potential for respiratory distress. Thus, all animals were monitored for signs of restraint stress (changes in grooming, feeding or defensive behaviours or demonstrating extreme reluctance to enter the exposure tubes or excessive attempts to escape restraint) and respiratory distress (such as coughing, nasal or eye discharge, sneezing, wheezing, laboured breathing, pale skin), and weighed frequently. None of the animals experienced these signs above the agreed humane threshold and all weights remained within normal ranges, so no animals were killed before their experimental time point.

The results achieved will inform hazard assessment and provide guidance on such exposures in humans.

Colindale

Table 4. Numbers of animals used, per species, at Colindale

Severity	Mice	Guinea pigs	Hamsters	Ferrets	Rats	Cotton rats	Rabbits	Turkeys	NHPs
Non-Recovery	0	52	0	0	0	0	0	0	0
Mild	50	0	0	4	0	0	0	25	0
Severe	4	0	0	0	0	0	0	0	0
Total	54	52	0	4	0	0	0	25	0

Guinea pigs

2023 saw the use of 52 guinea pigs. In influenza 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 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 four of the tests were positive, that is showing some signs of botulinum clostridium in the patients’ clinical sample and so these mice were classified as having experienced severe severity.

Forty-two mice were used to produce antisera The objective of this project is to produce reagents (substances used for biological or chemical analysis) and data for the diagnosis, control, or prevention of communicable (and other) diseases. The reagents are produced using animals in experimental procedures to produce antisera which is then used in non-animal laboratory tests for the control, prevention, surveillance and diagnosis of disease. All mice experienced only mild severity.

Turkeys

To conduct influenza assays, 95 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.