title: An update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.
abstract: BACKGROUND
  Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide.
  
  
  METHODS
  After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials.
  
  
  CONCLUSIONS
  It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.
authors.affiliation: Scientific Institute of Public Health(WIV-ISP-Site Ukkel), Program Host-Pathogen Interactions, Service Immunology, Brussels, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Romano
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001500:BCG Vaccine; D032581:Tuberculosis Vaccines