Abstracts (complete list) - Wissenschaft Online

Christiane Desel, Stefan H.E. Kaufmann
Tuberculosis: Efficacy of DNA vaccines encoding dormancyassociated
antigens
It is estimated that one third of the world’s population is latently infected with
Mycobacterium tuberculosis, the causative agent of tuberculosis. Of those 2 billion
people 5-10% will develop active disease during their lifetime. The infection claims 2
million lives every year and 9 million new cases are reported annually.
M. tuberculosis has a striking capacity to evade the host’s immune system and to
prevent its elimination. As a response to stress caused by a vigorous immune response
the bacteria induce a dormancy programme enabling survival within host macrophages.
But as soon as the immune surveillance fails, the dormant bacteria will be resuscitated
leading to active tuberculosis. The only available vaccine against tuberculosis is
Mycobacterium bovis BCG, one of the safest live vaccines known. However its protective
effect against pulmonary tuberculosis in adults is debatable and protection wanes with
time. Not only better pre-exposure vaccines to prevent infection in the first place but
also post-exposure vaccines for those individuals harbouring dormant bacteria are
urgently needed.
It is known that mycobacteria express different antigens during the dormant state as
compared to actively replicating ones and also the immune mechanisms to control
primary and latent infection differ. Post-exposure vaccines will have to be designed
based on antigens upregulated or solely expressed during dormancy. Dormancy is
linked to hypoxic conditions within the granuloma and surrounding tissue and the
dormancy survival regulator DosR has been identified as the primary factor which
mediates the genetic response to reduced oxygen levels as well as exposure to nitric
oxide. Here we examine the immunogenicity and efficacy of DNA vaccines based on
DosR-regulated antigens in murine models of persistent and latent Mycobacterium
tuberculosis infection.