Vaccines for Tuberculosis: Novel Concepts and Recent Progress

Abstract

SUMMARY Three-quarters of a century after the introduction of Mycobacterium bovis BCG, the first tuberculosis vaccine, new vaccines for tuberculosis are finally entering clinical trials. This breakthrough is based not only on advances in proteomics and genomics which have made the construction of new vaccines possible, but also on a greatly expanded knowledge of the immunology of tuberculosis. Here we review our current understanding of how Mycobacterium tuberculosis subverts or survives the host's immune response to cause disease and why the current vaccination strategy, which relies on BCG, is only partially successful in countering the pathogen. This provides a background for describing the new generation of vaccines designed to supplement or replace the current vaccine and the different approaches they take to stimulate immunity against M. tuberculosis.

B Cells Moderate Inflammatory Progression and Enhance Bacterial Containment upon Pulmonary Challenge withMycobacterium tuberculosis

“…Destruction of lung parenchyma by an exorbitant or dysregulated host response can cause lung scarring and subsequent pulmonary disability as well as cavitation, the latter is a process by which large numbers of bacteria breach mucosal barriers resulting in a highly contagious state (8,9). Consequently, a greater understanding of the factors that regulate the granuloma will be beneficial toward the development of novel TB therapies and vaccines aimed at stimulating protective immunity while minimizing pathologic sequelae of the host response (10).…”

“…Samples were then incubated on ice with CD19 magnetic beads (Miltenyi Biotec), and B cells were purified in accordance with the manufacturer's protocol. Purified lung B cells were resuspended to 10 7 cells/ml in complete RPMI and 100 l of this cell suspension was added to the upper chamber of a Transwell plate (Corning Costar). Lower chambers were filled with 600 l of medium alone, medium with 1 g/ml CXCL13 (R&D Systems), or medium with 1 g/ml CXCL13 and 15 g/ml anti-CXCL13 Ab (R&D Systems).…”

Natural carriers for application in tuberculosis treatment

“…86% of the cases are reported to occur both in Asia and Africa, especially in developing countries that lack adequate health conditions and face difficult medical access. Moreover, some disease conditions are known to increase the susceptibility of tuberculosis infection, such as the infection with human immunodeficiency virus (HIV), diabetes and chronic lung disease (Ranjita et al, 2011, Doherty andAndersen, 2005). In this manner, the disease is a major burden in developing countries, but it also remains present in many developed countries.…”

Pulmonary Tuberculosis and Mycobacterium Tuberculosis: Modern Molecular Epidemiology and Perspectives

“…There are urgent needs for control of the disease and thus it is essential to progress in applied research. Indeed, new vaccines [49,131], new drugs [23,134], and new diagnostics and advances in TB management [19,136] are urgently needed. Furthermore, we believe that it is no longer necessary to justify that basic research, including evolutionary and population genetics, experimental evolution, immunology, and cellular biology, is indispensable in order to progress in applied research.…”