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Vaccine Development

In humans, the live BCG vaccine against tuberculosis has been used since 1921 and well over three billion doses have been administered worldwide. As at the time of writing, this vaccine is accepted as a safe and effective preventative treatment, with no undue risks of serious long-term side effects. In children (and others), who are able to have it, it can provide an excellent preventive measure.

However, at best it is only about 70% effective and, in rare cases, at worst gives no protection at all. There is, therefore, a vital need for a new vaccine against TB in humans.

In addition, it is increasingly recognised that the spread of tuberculosis between wildlife, domestic animal species and man is best tackled by widespread vaccination. Of course these new vaccines will need to be considerably more reliable than the BCG vaccine to succeed in suppressing TB in an animal population.

As increasingly-sophisticated investigation and diagnostic techniques become available, the DNA of the tuberculosis organism is now being studied in detail and the entire genome sequence should be known soon. Advances in the molecular genetics of TB will almost certainly provide new and exciting prospects for the development of vaccines.

Examples of such techniques include DNA fingerprinting of the causative organism (Mycobacterium bovis), vaccine and diagnostic test development, model development and studies on the pathogenesis of tuberculosis in the badger. Isolates of the Mycobacterium bovis bacteria (from both cattle and wildlife species) are being "typed" using a relatively new technique called spoligotyping. These tests mean that national patterns of infection are now emerging, and researchers are beginning to understand that the ability to cause disease within the host varies with different spoligotypes. In time, these findings will improve understanding of the epidemiology of the disease and help in formulating control strategies.

Various "mutant" starins of Mycobacterium bovis are being studied in details and tests done to assess the extent to which they can be more effective than the BGC vaccine. This testing includes the use of laboratory modelling and the use of beneficial test animals (such as mice).

The World Health Organisation, for example, is confident that within 12 years a much improved vaccine to protect humans against TB will be available on a universal basis. The TB Research Group (part of the UK government's DEFRA department) is working closely with some of the leading researchers in human TB. Accordingly, they are confident that, with their efforts in co-ordinating the research and development work, it should be possible to take advantage of the rapid progress in human TB research to develop new animal vaccines.

Of course, one great weakness at present, is the relatively inaccurate diagnostics tests for TB. The test for TN in cattle is not very accurate, and produces a number of false positives and negatives. The current TB tests for badgers can only be done on a dead specimen.

Accordingly, the development of improved TB tests is also under way. Specifically, this includes antigen-specific lymphocyte proliferation assays and a gamma interferon assay. On the face of it, these strongly suggest that, with development, they will provide improved sensitivity over existing TB tests.

The scinetists working on TB-related work do not work enturely alone,; and other linked research is also being done into other problem cattle diseases, such as leptospirosis, digital dermatitis, cattle lameness, bovine viral diarrhoea, ruminant retroviruses and exotic and endemic mycoplasma.

Importantly, vaccine research strategies are now proposing to use methods which apply to any host species. The key objectives of the research programme include:

  • to identify the DNA of each individual strain of the TB virus
  • to produce live candidate vaccines by mutating existing strains, which should give better protection than BCG
  • to develop a diagnostic test to differentiate between vaccination and infection in cattle
  • to evaluate vaccines in all the key host species.

Hopefully, in this way, it will be possible to accelerate the way in which TB vaccines can be developed, and for those TB vaccines to be suitable for the vaccination of multiple-species.

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