These are exciting days in tuberculosis research. As we talk, more than fifteen independent teams all over the world are developing as many different vaccine candidates aimed either at substituting current, deficient BCG vaccine or at enhancing its effects.


Global pipeline for the development of new anti-tuberculosis vaccines. In the figure, there appear only the candidates which have already started clinical trials; among them, MTBVAC, developed by the group of Mycobacterium genetics of the University of Zaragoza, which is the first attenuated M.tb vaccine to enter clinical trials. (Image adapted from Aeras website. Aeras is a nonprofit organization devoted to development of new vaccines against tuberculosis)

Depending on the immunological principles underneath each candidature, it is expected that the age-groups on which eventual vaccination campaigns of each putative vaccine were different, which will influence the expected impacts of them regardless what their efficacies are. Another different question is where –and how– do the clinical trials devised to estimate vaccine efficacies at the final stages of the development pipeline should be undertaken, very particularly on what age groups must them be done. Ideally, high burden areas would be optimal places to observe vaccine protection, as they should allow efficacies estimations based on the recruitment of cohorts of reasonable size. However, some of these areas are often highly subjected to exposure to mycobacterial agents that can mask trial results or even block the vaccine performance. Furthermore, novel vaccines will hopefully unbalance –at a single host level– the struggle between pathogen and host at different stages of the immune response process, which will ultimately modify the pace at which individuals progress through the different stages of tuberculosis natural history; with differential epidemiological consequences. For these reasons, mathematical models of tuberculosis spreading will have to play a relevant role in the process of development of a new anti-tuberculosis vaccine, as the outcomes of these in-silico simulations for vaccine impact evaluations will probably be among the most relevant arguments for guiding the decision taking process related to the development of the different candidates and, ultimately, the final mass-production and market release of the one -or ones- offering a greatest impact. Finally, as relevant heterogeneities in what regards host-pathogen compatibility have been reported to play a relevant role, new vaccines will have to assure an homogeneous protection against all the main circulating strains of M.tuberculosis.

To assure accurate answers to these crucial, urgent questions, the already sophisticated mathematical models of tuberculosis spreading, can and must be improved, by explicitly addressing the influence of different factors to trans-national burden levels, as population mixing patterns, disparate scenarios of demographic evolution, heterogeneous associations between strain lineages and host ethnic profiles, etc.





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