Trends in Microbiology
OpinionTuberculosis vaccine development: recent progress
Section snippets
Animal models
To date, 170 candidates or combinations of candidates have been tested in these animal models (Fig. 1). Approximately 50% of these fall into the ‘subunit’ vaccine category, reflecting our increasing knowledge of the protein make-up of the bacillus and increased access to techniques to help identify the most immunogenic proteins. Other areas in which there has been substantial interest and progress are the DNA vaccines and recombinant vaccines. Approximately 75% of these candidates have been
Vaccine testing progress
Our current experience with the various types of vaccines tested so far is summarized in Table 1. We have no evidence of specific immunity being generated after vaccination with Mycobacterium microti or Mycobacterium vaccae, or other avirulent saprophytic mycobacteria. We have had good results using various auxotrophic mycobacteria, both derived from M. tuberculosis and BCG, but a drawback seems to be a lack of generation of memory immunity. What appears to be required is an auxotroph that can
Subunit vaccines
The most popular vaccine category is the subunit vaccines. Pools of proteins obtained from M. tuberculosis culture filtrate have been extensively tested, and individual proteins or mixtures of these proteins have provided good results 4. These pools or fractions contain proteins that are known to stimulate the memory-T-cell response specifically, a property that could be very useful and indeed seems essential. A drawback here, however, is that only a very few adjuvant vehicles are available
DNA vaccines
One of the most innovative areas in the field involves DNA vaccines, and multiple mycobacterial antigens have been targeted in this manner 11. Our best results to date have been obtained with a DNA vaccine targeting the mycolyl transferase enzyme Ag85A. This is protective in mice and, although it does not reduce the bacterial load in guinea pigs, it does prolong survival by stimulating a lymphocytic granulomatous response 12, 13.
Another potentially promising DNA vaccine is one that encodes the
Concluding remarks
In conclusion, this NIH-funded research program continues to test numerous innovative vaccines and strategies from multiple laboratories, giving rise to the optimism that new TB vaccines can indeed be produced. But it is a big jump from animal models to humans, and we must consistently emphasize that these are ‘models’, each of which has its own in-built advantages and disadvantages (Table 2). Even then, there is no guarantee new vaccines identified in these models will work (one can of course
Acknowledgements
This work was supported by NIH contract AI-75320.
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