Corporate report

Number of animals used: 2019

Updated 12 July 2021

The following table provides the numbers of animals used, per species, at our scientific campuses at Porton, Colindale and Chilton, in 2019.

Read more about how and why we use animals in research.

Site	Mice	Hamsters	Guinea pigs	Rabbits	Ferrets	Turkeys	Non-human primates (NHPs)
Porton	704	76	227	80	240	0	56
PBL	284	0	860	14	0	0	0
Chilton	1768	0	0	0	0	0	0
Colindale	12	0	51	0	8	12	0

PHE 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 2019 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 respond in a rapid and effective way to the urgent need to test novel interventions against the newly emerged coronavirus disease COVID-19. This provides assurance to the public that when a new infectious disease threat emerges Public Health England (PHE) is well rehearsed in assisting in the development of new countermeasures to protect the population.

Tuberculosis

Work has been performed to support the global effort to combat tuberculosis (TB). Refinements have been developed and implemented which include:

• the establishment of a model that uses exposure to only very low doses of Mycobacterium tuberculosis to evaluate vaccine efficacy (White 2020)
• work pioneering the use of high-frequency jet ventilation to minimise respiratory motion during the collection of Positron Emission Tomography-Computed Tomograph (PET-CT) images from macaques (Sharpe 2020)

Studies have been conducted to directly compare the immunogenicity and efficacy of the licensed Bacillus Calmette-Guérin (BCG) vaccination delivered by aerosol, or the conventional route of intradermal (ID) injection in the rhesus macaque ultra-low dose M. tuberculosis challenge model. The data is informing human experimental medicine studies and the study demonstrated the value of the ultra-low dose challenge model as a platform for the assessment of novel TB vaccine candidates and strategies. The identification of biomarkers of disease, or correlates of risk or protection would revolutionise TB vaccine development and efforts have continued towards this goal (Sibley 2019).

Publications

Use of high frequency jet ventilation as a refinement for imaging macaques with respiratory disease

Differences in monocyte: lymphocyte ratio and Tuberculosis disease progression in genetically distinct populations of macaques

Protective Efficacy of Inhaled BCG Vaccination Against Ultra-Low Dose Aerosol M. tuberculosis Challenge in Rhesus Macaques

Influenza

The project uses ferrets to test the Live Attenuated Influenza Vaccine (FluMist/Fluenz tetra) released for human use by the Food and Drink Administration (FDA) in the US, and by the European Medicines Agency (EMA) in the EU. Virus strains used in the vaccine are recommended seasonally by the World Health Organization (WHO). The team are responsible for performing several assays that aid in the seasonal selection and manufacture of the Live Attenuated Influenza Vaccine (LAIV).

The Attenuation Assay is a key batch release test for the LAIV which is currently offered to all 2 to 11 year olds in the UK. It is a qualitative test used to identify the attenuation (att) phenotype of Vaccine virus. The attenuated phenotype is characterised by detectable viral replication in the nasal turbinates of ferrets, and no or low levels of viral replication in the lung tissue. In contrast, wild-type influenza virus strains typically replicate in both nasal turbinates and lungs of ferrets, without evidence of restriction.

Additionally, Antisera and Immunogenicity tests are carried out following the WHO recommendations on the composition of influenza virus vaccines for the Southern Hemisphere in preparation for their recommendations for the Northern Hemisphere. These 2 assays aid in the strain selection for the following season’s vaccine.

Publications

Heterosubtypic cross-protection correlates with cross-reactive interferon-gamma-secreting lymphocytes in the ferret model of influenza

Metagenomic Nanopore sequencing of influenza virus direct from clinical respiratory samples

Emerging viruses

Mice have been used in the development of a murine model of Rift Valley Fever virus infection confirming susceptibility of wild-type mice to low doses of virus. This will allow PHE to assess the efficacy of interventions and comparison of viral pathogenesis from virus grown in mammalian and insect cell lines.

Additionally, mice have been used to assess the immunogenicity and efficacy of novel Hantavirus vaccines in preparation for phase I human clinical trials.

Publications

Hantavirus infection in type I interferon receptor-deficient (A129) mice

Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines

A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector

Towards quantification of protective antibody responses by passive transfer of the 1st WHO International Standard for Ebola virus antibody in a guinea pig model

Lineage-dependent differences of Zika virus infection in a susceptible mouse model are associated with different profiles of cytokines, chemokines, growth factors and acute phase proteins

A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model

Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans

Anthrax vaccine

During 2019, PHE’s medical countermeasure group evaluated the ability of a new experimental vaccine against anthrax. These studies assisted in helping to define the best dosage to use and the experimental vaccine has now progressed into human trials for immunogenicity and safety.

Clostridium difficile

PHE’s work on identifying therapies and treatments to protect the public from the disease caused by C. difficile continued in 2019 with assessments of delivery strategies and the protective effect of therapeutics and drugs in a model of infection. This data has been used by UK and US government entities.

Ebola

PHE continued to contribute towards the global effort to assess new and effective vaccines against Ebola by setting up an infection model. This development data was presented in international meetings and will be published in a peer-reviewed journal.

Q fever

PHE’s medical countermeasures group continued to advance the development of vaccines and drugs aimed at treating and preventing the disease caused by infection from Coxiella burnettii. This data will be published in a peer-reviewed journal.

Porton Biopharma Limited (PBL)

PBL’s work is focused on 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 mainly mice and guinea pigs, with more than half of this work classified as mild or moderate, while the remainder was classified as severe. Work is ongoing to replace such work with tests of mild severity using fewer animals.

Chilton

In total, 1768 mice were used to investigate the impact of environmental hazards on the body, including radiation, particles and chemical exposures as described in more detail below. The majority of these animals were classified as having mild severity with some classified as moderate. Understanding how environmental exposures impact different organ systems will help identify key biological processes, improve hazard identification and ultimately help develop appropriate interventions and/or guidelines.

Radiation

Ongoing experimental studies investigating how ionising radiation may contribute to leukaemia, intestinal tumour or cataract development have continued this year, using 773, 375 and 340 mice, respectively.

The leukaemia work has focused on the biological processes driving the development of acute myeloid leukaemia and has recently been published:

• Kras mutations and PU.1 promoter methylation are new pathways in murine radiation-induced AML
• Hematopoietic stem and progenitor cell responses to low radiation doses - implications for leukemia risk

The studies on intestinal tumours are examining if gamma radiation (administered over a short time period of 12 weeks) or x-rays (administered in 2 doses at different life stages) can lead to increased tumour numbers. Results will be published in a peer-reviewed journal once complete.

The cataract work has now been completed and the results are currently being drafted into 3 manuscripts that are expected to be published in the coming year, adding to the 2 that were published last year:

• Dotting the eyes: mouse strain dependency of the lens epithelium to low dose radiation-induced DNA damage
• Inverse dose-rate effect of ionising radiation on residual 53BP1 foci in the eye lens

Finally, 69 mice were used to investigate the effects of electromagnetic field exposure on circadian rhythms. The results from these studies were included in a transfer report for a DPhil student, and were due to be orally presented at a conference which was sadly cancelled due to the COVID-19 pandemic.

Particles

Inhalable particles are ubiquitous, present in household, work and outdoor environments. They include inorganic chemical (diesel exhaust and nanomaterials) as well as biological materials such as allergens (house dust mites), all with the potential to harm the lung and human health. During 2019, 166 mice were used to investigate how the lung and airways take up nanoparticles and respond to house dust mite and diesel particles. Results will be published in a peer-reviewed journal once complete.

Chemical exposures

In total, 45 mice were used to study the potential toxicities of e-cigarette vape. These mice were exposed to air only, e-cigarette vape with no nicotine, e-cigarette vape with a low concentration of nicotine or e-cigarette vape with a high concentration of nicotine. The results of this study established how best to expose the mice to ensure good animal welfare while achieving exposure levels comparable to human vapers.

Colindale

Mice

In 2019 12 mice were used for the detection of bacterial toxin assay (C Botulinum & C Tetani). This test is exclusively for testing clinical samples taken from patients who are suspected of having contracted the bacteria. Results of tests for botulism are also used for the identification of sources of infection and are of special importance to those involved with control of the food chain, that is environmental health officers and staff of the Food Standards Agency (FSA). These results provide vital, informed and evidence-based information for the identification of toxic food and allow its removal from the food chain to prevent further cases of the disease.

Ferrets

In 2019 8 ferrets were used to produce antisera for new and emerging strains of influenza, work which contributes to UK vaccine development. Antisera are produced using live animals and are only used if no such products exist in the commercial sector or in the research community. The antisera produced are used for surveillance, diagnosis, characterisation and provides information which will inform future vaccine development.

Turkeys

In total 12 turkeys were used to supply normal red blood cells to be used in influenza assays. As a reduction and refinement, the procedure is performed under general anaesthetic and birds are reused, each bird having a maximum of 9 bleeds spread over an 12-month period.

Guinea pigs

In total 51 guinea pigs were used in 2019. Guinea pig red blood cells are used for influenza H3 subtype assays and we also use their red blood cells in serology studies to determine the level of immune response in humans.