Tuberculosis and BCG
Our tuberculosis group carries out a range of services:
- quality control
- standardisation (written standards and physical standards)
- research and development
- projects on vaccines and assays
TB is the leading cause of death among curable infectious diseases. There are an estimated 9 million new cases and nearly 2 million deaths from TB around the world every year.
It is caused by bacteria belonging to the Mycobacterium tuberculosis complex and can affect almost any part of the body. The most common form is pulmonary TB. Non-respiratory forms of TB are more common in children from areas where TB is prevalent and in people with impaired immunity. It is transmitted through infectious droplets coughed by patients with pulmonary TB.
Vaccination and treatment
TB can be prevented in many developed countries by immunisation with the BCG vaccine which contains live attenuated bacteria derived from M. bovis in lyophilised formulation. However, the BCG vaccine is much less effective in developing countries, where TB can usually be treated with a combination of specific antibiotics, except for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases.
Latent TB infection may be reactivated, particularly if someone’s immune system is weakened – for example by diseases such as HIV-AIDS, medical treatments like cancer chemotherapy or corticosteroids, and old age. Currently there is no licensed vaccine to prevent latent TB.
Scientists in NIBSC took part in the World Health Organisation (WHO) BCG working group and played a key role in revising the current WHO recommendations to assure the quality, safety and efficacy of BCG vaccines.
NIBSC has also contributed to the European Pharmacopoeia monographs for BCG vaccine and BCG for immunotherapy.
Following recommendations from international experts in WHO consultation meetings on BCG vaccines, the WHO 1st international reference preparation for the BCG vaccine established in 1965 has been replaced with sub-strain specific BCG Reference Reagents. NIBSC coordinated the international collaborative studies of four reference reagents for the BCG vaccine of different sub-strains.
They have been adopted by WHO Expert Committee on Biological Standardisation (ECBS) and are now available for distribution. Together with the international standards of various Tuberculin PPD, these reference reagents are available in the NIBSC catalogue.
The lyophilised BCG product is currently the only licensed TB vaccine. It is also commonly used in immunotherapy to treat superficial bladder cancer in the UK and is tested at NIBSC for batch release. The assays used to control the quality of this product – set out in the European Pharmacopeia – are very similar to those for the lyophilised BCG vaccine product. The control tests used in NIBSC include in vitro tests for:
- appearance and solubility
- identity (multiplex polymerase chain reaction (PCR) assay)
- potency (cultural viable count assay)
We also critically evaluate the manufacturing protocol and certificate of analysis.
Research and development
Our scientists collaborate with many UK and European expert groups as part of different EU-funded consortia, currently including:
We are also the project coordinator of the EURIPRED consortium.
Projects to develop new TB vaccines
Many promising new TB vaccine candidates have been developed in the last decade. Since 2000 NIBSC scientists have collaborated with other experts on EU-funded projects and consortia, including:
These projects aimed to integrate the European efforts to develop novel TB vaccine candidates and forward these vaccines to small scale, Phase 1 human clinical trials in Europe and Africa.
NIBSC has a well-established murine aerosol challenge model for laboratory evaluation of new TB vaccine candidates in terms of protection against M. tuberculosis infection. This model has been used for contract testing and grant-funded research to screen new candidates at the discovery stage of product development, and for head-to-head comparison of various vaccine candidates within the NEWTBVAC consortium.
Other R&D activities include:
- establishing laboratory assays for new TB vaccine characterisation and for quality control purposes
- basic research to underpin quality, safety and efficacy studies of TB vaccines within a regulatory framework
Projects on immunological and functional assays
NIBSC scientists use various immunological techniques – such as flow cytometry, ELISpot and cytokine ELISA – for evaluation of immunological responses of TB vaccines. NIBSC was part of the TRANSVAC (European Network of Vaccine Research and Development) project, collaborating with the University of Oxford and London School of Hygiene & Tropical Medicines (LSHTM) to harmonise these assays. Relevant reference reagents were generated for research uses, such as interferon gamma-positive/negative lyophilised human PBMCs for flow cytometry.
In the EURIPRED project we will collaborate with UK and European expert groups in assay harmonisation of other immunological assays, such as Luminex bead-based assays.
The main areas where we give advice are:
- providing regulatory advice and recommendations on vaccine safety, quality and characterisation to vaccine developers and manufacturers
- facilitating and helping vaccine developers throughout the pre-clinical development process to bring vaccine candidates to Phase I clinical trial studies
- establishing guidelines and principles for harmonising immune assays used in clinical trials of TB vaccines