[New antituberculosis vaccines]

Abstract

Today, only one type of vaccine is available to protect against tuberculosis. This vaccine, called Bacille Calmette-Guérin (BCG) was developed approximately 100 years ago and has been administered at least 3 billion times. Initial multicenter studies have indicated an up to 93% efficacy against childhood tuberculosis mortality. Subsequently, many studies on BCG efficacy have been carried out, with highly variable results, ranging from 0 to 90% efficacy. The reasons for this heterogeneity are not well understood. Large clinical studies have shown that booster vaccinations with BCG do not improve the BCG efficacy. Therefore, new vaccines are urgently needed. Today, there are essentially two lines of efforts being pursued in several laboratories. One of them aims at replacing BCG with superior vaccines. This strategy focuses either on improving existing BCG by constructing strains that overproduce certain protective antigens and/or by improving its immunogenicity, or on starting anew by genetically attenuating virulent Mycobacterium tuberculosis. The second line of research aims at adding onto BCG vaccination, such as a heterologous prime-boost strategy. For this strategy BCG is used as a first vaccine, followed by individual antigens as a booster. These antigens can be presented in several different ways, and preference is currently given to the so-called latency antigens. Both approaches have yielded encouraging results in animal models, and some of them have now entered clinical trials. Although still far from human applications, it is hoped that these strategies will ultimately help to reduce the enormous burden that is caused by tuberculosis.