N. S. Kelkar, N. C. Curtis, U. S. Khanwalkar, O. G. Palmer, T. P. Lahey, W. Wieland-Alter, J. E. Stout, E. C. Larson, S. Jauro, C. A. Scanga, P. A. Darrah, M. Roederer, R. A. Seder, C. F. von Reyn, J. Lee, M. E. Ackerman
Development of an effective tuberculosis (TB) vaccine has been challenged by incomplete understanding of specific factors that provide protection against Mycobacterium tuberculosis (Mtb) and the lack of a known correlate of protection (CoP). Using a combination of samples from a vaccine showing efficacy (DarDar [NCT00052195]) and Bacille Calmette-Guerin (BCG)-immunized humans and nonhuman primates (NHP), we identify a humoral CoP that translates across species and vaccine regimens. Antibodies specific to the DarDar vaccine strain (M. obuense) sonicate (MOS) correlate with protection from the efficacy endpoint of definite TB. In humans, antibodies to MOS also scale with vaccine dose, are elicited by BCG vaccination, are observed during TB disease, and demonstrate cross-reactivity with Mtb; in NHP, MOS-specific antibodies scale with dose and serve as a CoP mediated by BCG vaccination. Collectively, this study reports a novel humoral CoP and specific antigenic targets that may be relevant to achieving vaccine-mediated protection from TB.