In the case of vaccines capable of stopping infection, antigen choice is straightforward but, due to the nature of Mtb infection, it is likely that vaccines that prevent disease rather than infection will be more easily achievable and, in this situation, antigen choice is critical. In TB, vaccines can be designed to stop infection, to prevent development of disease or to reduce the consequences of disease. While there are practical considerations regarding how best to produce and deliver antigens, these are secondary to choosing specific antigens based on their ability to be detected by the immune system during infection. The choice of antigens in vaccine development is fundamental to efficient design. Vaccination is a key tool in the cost-effective control of infectious disease however, development of a TB vaccine has proven difficult, although some progress is being made recently.
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Furthermore, up to a quarter of the world’s population are thought to be infected with Mtb with approximately 56 million of those at high risk of developing TB. Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), remains a leading cause of death from a single infectious agent and is estimated to kill approximately 1.2 million people every year. These data indicate the need to assess both protective and pathogenic responses when investigating subunit vaccine activity. The weight loss was associated with an imbalance between TNFα and IL-17 transcription in the lung upon challenge. We found that in both a low pattern recognition receptor (PRR) engaging adjuvant and a high PRR-engaging adjuvant (MPL/TDM/DDA) the triple-antigen fusion could reduce the bacterial burden, but also induced weight loss in the mice upon aerosol infection.
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We generated a triple-antigen fusion containing the virulence-associated EsxN (Rv1793), the PPE42 (Rv2608), and the latency associated Rv2628 to investigate the balance between bacterial reduction and weight loss in an animal model of aerosol infection. Subunit vaccines containing antigen require adjuvants to drive appropriate long-lived responses. Development of new vaccines requires identification of antigens that are both spatially and temporally available throughout infection, and immune responses to which reduce bacterial burden without increasing pathologic outcomes. BCG is effective in limiting childhood disease, but adult TB is still a major public health issue. Tuberculosis vaccines capable of reducing disease worldwide have proven difficult to develop.