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What about tuberculosis makes it difficult to produce a safe vaccine that is effective at producing an immunogenic response in >99% of individuals against all strains of the bacteria?

I am aware of the BCG vaccine which has a variable efficacy depending on how it is measured and am aware of the 4 current vaccine candidates (MVA85A, rBCG30, 72F fusion protein, and ESAT6-Ag85b fusion protein). I am curious about the very specific question of aspects of the bacteria that make the TB vaccine difficult.

Many, many thanks.

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  • $\begingroup$ The fact that it stays dormant for a while and resides in lungs, which makes it difficult for drugs to access it and diagnose its presence until its late! $\endgroup$ Oct 16 '14 at 9:16
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Thats an interesting and complex question. First, Mycobacteria tuberculosis is present for a long time in the human population and evolved to evade our immune system. One of the keys are glycolipids and sugars which are part of the bacterial cell wall. These either help suppressing an immune response or help the bacteria to enter host cells in which they can stay without being identified by the immune system. See references 1-3 for details on this topic.

Then most tuberculosis infections are hold of by the immune system, mostly they come up, when the carriers immune system is compromised. M. tuberculosis can successfully hide inside macrophages and multiply there and start an infection from this hiding place. See references 4 and 5 for more details here.

One of the main problems with the development of new vaccines is that this takes quite a long time from successful experiments in the lab to the availability of a usable vaccine. Tuberculosis has been neglected here for decades. Then the market for such a vaccine wasn't deemed lucrative enough from the pharma companies, as this is mostly important for poor and developing countries. For use there, the vaccine needs to be cheap and easy to administer. Additionally humans are the main host for M.tuberculosis which makes chossing appropriate animal models for research and testing not an easy task.

The development of novel vaccine candidates follow different routes. First, there are live vaccinations, which mainly consist of modified strains of the BCG vaccine strain. Then there are vaccines in the development which are supposed to support the immune answer by BCG and finally, there are vaccines which are independent of BCG and are mostly composed from proteins of the outer bacterial cell wall. For an overview about this field, I can recommend the review articles 6 and 7, if you want to go deeper in the field, also the references 8-10.


References

  1. Mycobacterium tuberculosis Cell Wall Glycolipids Directly Inhibit CD4+ T-Cell Activation by Interfering with Proximal T-Cell-Receptor Signaling
  2. Divergent Effects of Mycobacterial Cell Wall Glycolipids on Maturation and Function of Human Monocyte-Derived Dendritic Cells
  3. Interactions between Mycobacterium tuberculosis and host cells: are mycobacterial sugars the key?
  4. Annulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis
  5. Macrophages Play a Dual Role during Pulmonary Tuberculosis in Mice
  6. Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?
  7. Vaccine against tuberculosis: what’s new
  8. Tuberculosis vaccines: past, present and future.
  9. Childhood tuberculosis: old and new vaccines.
  10. Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis
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