Current approaches toward identifying a correlate of immune protection from tuberculosis

Mycobacterium tuberculosis kills more people than any other pathogen. Vaccination is the most cost-effective control measure for any infectious disease. Development of an effective vaccine against tuberculosis is hindered by the uncertain predictive value of preclinical animal models, incomplete understanding of protective immunity and lack of validated immune correlates of protection (COP).

Here we review what is known about protective immunity against M.tb, the preclinical and clinical cohorts that can be utilized to identify COP, and COP that have been identified to date.

The identification of COP would allow the rational design and development of vaccine candidates which can then be optimized and prioritized based on the induction of these immune responses. Once validated in field efficacy trials, such COP could potentially facilitate the development and licensure of vaccines, in combination with human efficacy data. The identification and validation of COP would represent a very significant advance in TB vaccine development. Every opportunity to collect samples and cohorts on which to cross-validate pre-existing COP and identify novel COP should be exploited. Furthermore, global cooperation and collaboration on such samples will ensure that the utility of such precious samples is fully exploited.