Multivariate analysis establishes airway T cells as a correlate of IV BCG-mediated protection against tuberculosis in rhesus macaques

The attached files, including the figures and code scripts, are the multivariate analysis part involved in the following paper:

Multivariate analysis establishes airway T cells as a correlate of IV BCG-mediated protection against tuberculosis in rhesus macaques

Mycobacterium tuberculosis (Mtb) is a leading cause of death by infectious disease. Defining immune correlates of protection will inform vaccine development. We performed a dose-ranging study of intravenous (IV) BCG vaccination in macaques that generated a range of immune responses and protection against Mtb challenge. 17 of 34 macaques had no detectable infection based on PET CT imaging, granuloma formation, pathology, or Mtb burden. Multivariate analysis incorporating longitudinal cellular and humoral immune parameters uncovered an extensive and highly coordinated immune response from bronchoaveolar lavage (BAL). A minimal signature that predicted protection contained four BAL immune features, of which three remained significant after correcting for dose: the frequency of CD4 T cells producing TNF with IFNg and TNF with IL-17, and the number of NK cells. Blood immune features were less predictive of protection. We conclude that CD4 T cell immunity in the airway correlate with protection following IV BCG.