Deciphering protective immunity against tuberculosis: implications for vaccine development

The development of more effective tuberculosis (TB) vaccines is essential for the global control of TB. Recently, there have been major advances in the field, but an important hindrance remains the lack of correlates of protection against TB. This requires each vaccine candidate to undergo clinical efficacy trials based on data from animal protection studies, but the results from animal models do not necessarily predict efficacy in humans.

In this review we summarize our current knowledge of immune mechanisms that may contribute to protective immunity against TB following vaccination and relate these to protective efficacy in animal models and recent clinical trials. Although some initial trials did not reproduce protection against TB in humans, recent trials have demonstrated promising efficacy for three vaccine approaches.

Although CD4⁺ T lymphocytes are essential for protection against TB, there is no clear correlation between conventional CD4⁺ or CD8⁺ T cell responses and protective efficacy of TB vaccines. Recent attention has focused on other immune responses, including donor unrestricted T cells, B lymphocytes, and antibodies. Prospective studies on samples from vaccinated individuals protected in recent trials will allow evaluation of these alternative immune mechanisms as potential correlates of protection.