Recent developments in the epidemiology and management of tuberculosis – new solutions to old problems?

Figures & data

Table 1 Potential candidates for new antituberculosis drugs

Drug candidate	Mechanism	Attributes
TMC-207	Targeting of ATP synthase	Efficacy proven in animal model and clinical trial; novel pharmaceutical target
PNU-100480	Linezolid-analog, targeting ribosome	Novel pharmaceutical target
SQ-109	Ethambutol-analogue, targeting cell-wall synthesis	Efficacy proven in animal model
OPC-67683 and PA-824	Prodrug; bioreactive activation	Potentially effective against latent tuberculosis

Abbreviation: ATP, adenosine triphosphate.

Table 2 Pipeline of vaccine candidates that are currently in clinical trials

Category	Vaccine candidate	Mechanism	Clinical trial
Live vaccines as BCG replacement	AERAS-422	Expression of perfringolysin O to allow escape into the cytoplasm Expression of immunodominant antigens 85A, 85B and Rv3407	Phase 1
	rBCGΔureC:Hly	Listeriolysin enables BCG to escape from the endosome to enhance antigen cross-presentation UreaseC-deficiency ensures optimal pH for listeriolysin activity	Phase 1 completed
Subunit vaccines as BCG boost: viral vectors	Ad5Ag85A	Adenovirus type 5 expressing mycobacterial antigen 85A	Phase 1
	AERAS-402	Adenovirus type 35 expressing 85A, 85B and TB10.4 as a fusion protein	Phase 11
	MVA85A	Modified vaccinia virus Ankara expressing antigen 85A	Phase 11b
Subunit vaccines as BCG boost: protein/adjuvant formulations	HyVac4	Fusion protein of TB10.4 with antigen 85B plus adjuvant MPL or IC31	Phase 1
	Hybrid 1	Fusion protein of ESAT-6 with antigen 85B plus adjuvant CAF01 or IC31	Phase 1
	M72	Fusion protein of Mtb32 and Mt39 plus adjuvant AS02A	Phase 11a completed
Therapeutic vaccines	Mycobacterium vaccae	Whole-cell vaccine (inactivated)	Phase 1
	RUTI^®	Detoxified liposomal cellular fragments of M. tuberculosis	Phase 1 completed

Abbreviation: BCG, Bacille Calmette-Guérin.