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