The Health Protection Agency's role is to provide an integrated approach to protecting UK public health through the provision of support and advice to the NHS, local authorities, emergency services, other Arms Length Bodies, the Department of Health and the Devolved Administrations. The Agency was established as a special health authority (SpHA) in 2003. On 1 April 2005, the Agency was established as a non-departmental public body, replacing the HPA SpHA and the National Radiological Protection Board (NRPB) and with radiation protection as part of health protection incorporated in its remit. In 2009 NIBSC became a Centre of the HPA. The HPA has a large network of approximately 3000 staff based at three major centres (Colindale, Porton Chilton and NIBSC) and regionally and locally throughout England.

The Health Protection Agency, Centre for Emergency Preparedness and Response (CEPR, formerly CAMR) has a long history of research into microbial pathogens (pathogenicity studies, animal models, vaccine development and GMP production of materials for clinical trials, and derivation of biotherapeutic molecules from micro-organisms), with a skilled staff base, facilities for the investigation of pathogens up to and including ACDP level 4 with extensive ACDP level 3 facilities.  

CEPR has UK MHRA GLP accreditation, cGMP production and UK Government Home Office animal certification, US Government Office of Laboratory Animal Welfare (OLAW) certification for all public health affairs supported activities involving live invertebrate animals. Other capabilities include quality control (QC) and quality assurance (QA) facilities and personnel; and qualified shipping, receiving, and storage facilities.

CEPR has invested in developing bespoke high containment facilities for in-vivo studies which are complemented with capabilities for X-ray, haematology, clinical chemistry, T-cell immunology and flow cytometry. There has also been a focused investment in facilities and expertise to enhance the capability to infect animals by the aerosol route with ACDP level 3 pathogens, this includes plethysmography, enhanced aerosol sampling equipment and bespoke aerosol challenge isolators. Staff at CEPR have worked with non human primate models for over 20 years, with experience of SIV/macaque model for AIDS.

CEPR has an extensive TB research programme funded by the Health protection Agency UK, the EU Framework 6 and 7 programmes and various commercial partners. The focus of the Programme is on vaccine development & evaluation, and identification of targets for therapeutics, and uses a range of TB aerosol challenge animal models (mice, guinea pig and non-human primates). These models are scarce, and CEPR has the largest TB vaccine evaluation capability in Europe, and has close links to the other major global TB vaccine testing centres. The overall aims of the programme are:

• The development of new effective TB vaccines through (a) the provision of independent data on the efficacy of lead vaccine candidates in animal models of primary disease, (b) the identification of correlates of protection/biomarkers of disease, and (c) the evaluation of the efficacy of novel in-house TB vaccines.
• A detailed understanding of the biology of “latency” in Mycobacterium tuberculosis and exploitation of this knowledge to identify diagnostic antigens, as well as potential novel vaccine and drug targets.

• The application of novel in vitro and in vivo models in which to evaluate new anti-TB drugs, singly and in combination.

Main staff involved in the project

Dr Sally Sharpe provides expertise in non-human primate models of infectious disease and in the detailed assessment of immune responses to both vaccination and induced disease in the models. The studies will be supported by experts in non-human primate care/welfare, and post-graduate researchers who will conduct the immunological analyses. Over the past 7 years, Dr Sharpe’s group has established a wide range of immunological analysis appropriate for the dissection of the immune response to TB infection and TB vaccines using both peripheral blood and tissue samples from NHP. An expertise in flow cytometry has been developed within the group and the capability to perform intracellular cytokine staining, immunophenotyping and cell population dynamics.

Mr Michael Dennis is the Scientific Leader of the Biological Investigations Groups which is the specialised facility in which all the animal studies will be conducted. He has extensive experience in animal models using a wide range of infectious agents and in developing biocontainment strategies for the safe use of these pathogens in a number of animal species.  Mr Dennis has over 20 years of experience in the use of non-human primate models, with particular reference to AIDS, TB and biodefence models. He is currently Head of the HPA Primate Strategy Group which co-ordinates NHP breeding and experimental use within the Health Protection Agency.

Dr Ann Rawkins nee Williams provides expertise in aerobiology, animal model development and brings 15 years of experience in the pre-clinical evaluation of TB vaccines and a particular expertise in guinea pig and aerosol infection models of bacterial infections.

Transnational Access Services Offered

HPA will perform transnational service activities to evaluate the immunogenicity and safety of vaccines in immunocompromised rhesus macaques. Supporting these service activities, Networking and R&D activities will be aimed at improving the validity of the animal studies to clinical trials and to keep pace with technology developments, including development of reagents and assay systems for guinea pigs.

HPA-CEPR will conduct studies to evaluate the immunogenicity and safety of vaccines in immunocompromised rhesus macaques. Rhesus macaques will be infected with a particular strain of simian immunodeficiency virus (SIV) with a well-characterised capacity to immunosuppress the animals. At a pre-determined time point, the animals will be given the test vaccine and regular clinical observations and blood sampling will enable the effects of the vaccine on the animal in terms of immunological and clinical / pathological read-outs, to be determined. At the end of the study period a detailed post-mortem examination of the animals will be conducted and samples taken to comprehensively assess the impact of vaccination in an immunocompromised host. SIV-infected but unvaccinated animals and uninfected, vaccinated animals will serve as controls to determine the following:

• Any adverse clinical effects of the vaccine,
• Any pathological effects of the vaccine, including exacerbation of the SIV infection, accumulation of the vaccine in any organs,
• Effects of the immunosuppression on immune response to the vaccine.

The Health Protection Agency, Centre for Emergency Preparedness and Response (CEPR-HPA) is a global leader in translational research related to infectious diseases and brings specialist expertise in high containment in-vivo models to the TRANSVAC consortium.