Systems approach to tuberculosis vaccine development

Tuberculosis is both highly prevalent across the world and eludes our attempts to control it. The current bacillus Calmette-Guérin vaccine has unreliable protection against adult pulmonary tuberculosis. As a result, tuberculosis vaccine development has been an ongoing area of research for several decades. Only recently have research efforts resulted in the development of several vaccine candidates that are further along in clinical trials. The majority of the barriers surrounding tuberculosis vaccine development are related to the lack of defined biomarkers for tuberculosis protective immunity and the lack of understanding of the complex interactions between the host and pathogen in the human immune system. As a result, testing various antigens discovered through molecular biology techniques have been only with surrogates of protection and do not accurately predict protective immunity. This review will address new discoveries in latency antigens and new next-generation candidate vaccines that promise the possibility of sterile eradication. Also discussed are the potentially important roles of systems biology and vaccinomics in shortening development of an efficacious tuberculosis vaccine through utilization of high-throughput technology, computer modelling and integrative approaches.