Corporate report

Number of animals used: 2021

Updated 12 July 2023

The following tables provide the numbers of animals used, per species, at our scientific campuses at Porton, Colindale and Chilton, in 2021.

Site Mice Hamsters Guinea pigs Rats Rabbits Ferrets Turkeys Non-human primates (NHPs)
Porton 1,248 610 270 0 0 115 0 71
PBL 30 0 1,353 0 23 0 0 0
Chilton 1,868 0 0 48 0 0 0 0
Colindale 12 0 18 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 2021 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 (COVID-19).

This has provided a rare capability to international funders such as Coalition for Epidemic Preparedness Innovations (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, 62 experienced only mild or non-recovery procedures with 9 classified as moderate. For other species, 43% of procedures were classified as mild, 55% as moderate and 2% as severe.

Tuberculosis

Work in 2021 has been performed to support the global effort to combat tuberculosis.

NHP studies

Studies using non-human primate (macaque) models of Mycobacterium tuberculosis (M. tuberculosis) infection have supported the clinical development of new TB vaccine candidates by providing immunogenicity and efficacy data critical for progression to clinical deployment. Proof of concept for a new model for the evaluation of vaccine strategies against TB reactivation was also established.

Previously work at Porton identified differences between macaque populations in relation to their susceptibility to Mycobacterium tuberculosis infection and materials archived from previously conducted studies have been used to explore potential mechanisms behind the improved control identified in cynomolgus macaques and the implications of natural resistance for TB vaccine evaluation.

Previously stored materials also provided opportunities to explore the immune responses induced following vaccination with Bacillus Calmette-Guérin (BCG) vaccine that may play roles in protection from M. tuberculosis infection or cancer and the impact of age at vaccination on the responses induced.

The expertise established through studies we conducted to inform human experimental medicine studies that focused on the re-purposing of BCG vaccine by altering the route of delivery enabled us to respond in a rapid and effective way to test the potential off-target effects reported for BCG as part of the urgent response needed against the newly emerged COVID-19.

Guinea pig and mouse studies

The continuing spread of drug-resistant tuberculosis (TB) is 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.

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

TB and SIV co-infection: a model for evaluating vaccine strategies against TB reactivation in Asian origin cynomolgus macaques: a pilot study using BCG vaccination

Differences in host immune populations between rhesus macaques and cynomolgus macaque subspecies, in relation to susceptibility to Mycobacterium tuberculosis infection

Dynamics of macrophage, T and B cell infiltration within pulmonary granulomas induced by Mycobacterium tuberculosis in 2 non-human primate models of aerosol infection

High dose aerosol challenge with Mycobacterium tuberculosis fails to overcome BCG vaccination-induced protection in cynomolgus macaques of Chinese origin: implications of natural resistance for TB vaccine evaluation

Induction of functional specific antibodies, IgG-secreting plasmablasts and memory B cells following BCG vaccination

BCG induces superior anti-tumour responses by Vδ2+ T-cells compared to the aminobisphosphonate drug Zoledronic acid

Characterization of the infant immune system and the influence and immunogenicity of BCG vaccination in infant and adult rhesus macaques

The potential of microdialysis to estimate rifampicin concentrations in the lung of guinea pigs

Pathogenomic analyses of Mycobacterium microti, an ESX-1-deleted member of the Mycobacterium tuberculosis complex causing disease in various hosts

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.

SARS-CoV-2

In brief, predominantly 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. 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 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 the World Health Organization (WHO) and events sponsored by the European Centre for Disease Prevention (ECDC) and the Global Forum for TB vaccines in Toulouse.

Publications

Influence of aerosol delivered BCG vaccination on immunological and disease parameters following SARS-CoV-2 challenge in rhesus macaques

Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19

ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

Development of a hamster natural transmission model of SARS-CoV-2 infection

One or 2 dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model

A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19

Clostridium difficile

UKHSA works on identifying therapies and treatments to protect the public from the disease caused by C. difficile continued in 2021 with assessments of the protective effect of therapeutics and drugs in a model of infection.

The work provided evidence to government bodies as to the effectiveness or otherwise of new potential drugs.

Other infections of global importance

Ebola

Model development of Ebolavirus infection in the ferret is a substantial refinement over NHP models used at other research establishments. This may prove useful in the development and assessment of new therapeutics and vaccines in the future.

Q fever

There remains no effective and safe vaccine for use in humans against Q fever and the work performed under this project has contributed to finding the core components of immunity that a putative vaccine would need to elicit. In addition, work carried on site has contributed to the body of knowledge on the safe and effective use of antimicrobial or antibiotic drugs for the treatment and prevention of human Q fever.

Work has been conducted to adapt Lassa virus to the guinea pig and obtain a relevant infectious dose to provide a preclinical model for the assessment of interventions needed against this important haemorrhagic fever virus. Animal work has enabled the testing of serological standards to provide a standardised antibody level that elicits protective responses for Lassa virus, Rift Valley Fever virus and Crimean-Congo Haemorrhagic Fever (CCHF) virus.

These protective antibody titres will help to inform on which vaccine candidates will likely be protective, so refining those that progress to testing by challenge with infectious virus. Studies to assess the efficacy of cost-effective protein subunit vaccine candidates against CCHF virus have been undertaken, supporting UK-funded activity on vaccines for diseases with a likelihood to cause epidemics.

For work on Chikungunya virus, a study has been conducted to look at the susceptibility of different mouse strains to ascertain the most relevant model for the assessment of protective immunity.

Publications

Evaluation of the efficacy of Doxycycline, Ciprofloxacin, Levofloxacin, and Co-trimoxazole using in vitro and in vivo models of Q fever

Finafloxacin, a novel fluoroquinolone, reduces the clinical signs of infection and pathology in a mouse model of Q fever

Dose-dependent response to infection with ebola virus in the ferret model and evidence of viral evolution in the eye

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 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

During 2021, UKHSA Chilton used a total of 1,916 animals in the projects detailed below. The majority of these animals suffered no or mild harm, with some suffering moderate harm.

Radiation

Radiation-induced cardiovascular disease

A total of 286 mice were used to complete investigations on the effect of age on radiation-induced heart disease. This included animals used for breeding as well as those used for the remainder of the studies (continued from last year).

Radiation-induced leukaemogenesis

A total of 1,129 mice were used to examine how radiation can lead to the development of leukaemia. Most (903) of these animals were used for breeding in preparation for producing embryos for cold storage, which began in January 2021. This has enabled 4 out of 5 mouse strains to be stored so maintenance breeding will not be required when the strains are not in use.

This will significantly reduce the number of animals used in the future. The remaining (226) animals were used in the continued longer-term studies on radiation-induced leukaemia.

A paper from this work was published online.

Radiation-induced intestinal carcinogenesis

A total of 304 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.

Biological effects of electromagnetic fields

The study used 99 mice to continue to study the effect of magnetic fields on the body’s internal clock (circadian rhythm), which involved tracking sleep and activity behaviours during magnetic field exposures prior to examining changes in the expression of genes controlling circadian rhythm.

Toxicity of inhaled environmental particles

A total of 48 rats were used to examine how steel particles radiolabelled with tritium are distributed throughout the body following inhalation. This study aims to improve knowledge on tritium management in fissions and fusion facilities.

Note, a further publication including animals used in previous years to investigate the formation of cataracts as a result of low-dose ionising radiation was also released this year.

The changes to EU basic safety standards that came into force in 2018, reducing the occupational ionising dose limit for the lens of the eye from 150 to 20 mSv/year, were predominantly based on epidemiological (population-based) studies. At this point, very little was known about the underlying biological processes driving low-dose radiation cataract formation.

Research in this area was thus highlighted as a high priority for the International Commission on Radiological Protection (ICRP).

The animal work performed at UKHSA in previous years has made a significant contribution to the LDLensRad study, a project funded by the EU’s Concerted Programme on Radiation Protection Research (CONCERT) and set up to assess differences in dose, dose rate, but also age, sex, and genetic background-based responses to ionising radiation.

This has provided a huge amount of new understanding in terms of how ionising radiation at low doses contributes to radiation cataract as highlighted in the papers in the publication this year.

This, in turn, is expected to contribute to the forthcoming revisions to the system of radiation protection, currently under consideration by the ICRP.

Metabolic effects of sunlight

Two mice have been used so far in the planned new study of 30 animals to investigate how long wavelength (non-hazardous) UV light can affect metabolism via modulation of the immune system. This pilot study validates claims that sunlight may have additional positive effects on health beyond the associated benefits of vitamin D.

Potential toxicities of e-cigarettes

A total of 48 mice were used in the continued study of the potential production of harmful chemicals from nicotine within e-cigarette aerosols. These animals were used in a second pilot study to determine if eating increased amounts of nitrates or nitrites can lead to the production of greater levels of harmful compounds from nicotine within e-cigarette aerosols. Such information will help to further inform and improve public health advice around vaping.

Colindale

Work at Colindale was mainly focused on the provision of biological reagents for vital assays used in both clinical diagnosis and in vaccine development. In addition, clinical samples from patients with suspected infection with toxin-producing bacteria were tested in mice.

Guinea pigs

2021 saw the use of 18 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.

Mice

In total, 12 mice were used in 5 tests to detect bacterial toxins (Clostridium botulinum and Clostridium tetani). The test is used for testing clinical samples taken from patients suspected of having contracted the bacteria.

Turkeys

To conduct influenza assays, 12 turkeys were used to supply normal red blood cells.

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.