Tuberculosis vaccines: time to reset the paradigm?

To cite: Lalvani A, Sridhar S, von Reyn CF. Thorax Published Online First: [please include Day Month Year] doi:10.1136/ thoraxjnl-2013-203456 ABSTRACT Development of a more effective tuberculosis vaccine is a global public health priority. The first clinical efficacy trial of a new tuberculosis vaccine candidate in over 45 years recently reported its results. Unfortunately, the vaccine, MVA85A, showed no improved efficacy over BCG in preventing tuberculosis disease or infection in 2797 infants. This disappointing result has far-reaching ramifications because the majority of TB vaccine candidates in clinical trials broadly aim to induce the same type of immune responses as MVA85A. This compels close re-examination of the immunological paradigm underpinning the development of most new tuberculosis vaccines. Progress will require frank appraisal of the gaps in our understanding of protective immunity and appropriate use and interpretation of the available animal models. Identifying correlates of protection by dissecting immune responses induced by existing partially effective vaccines may be a good place to focus renewed efforts.