Quest for correlates of protection against tuberculosis

Kamlesh Bhatt, Sheetal Verma, Jerrold J. Ellner, Padmini Salgame

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


A major impediment to tuberculosis (TB) vaccine development is the lack of reliable correlates of immune protection or biomarkers that would predict vaccine efficacy. Gamma interferon (IFN-γ) produced by CD4+ T cells and, recently, multifunctional CD4+ T cells secreting IFN-γ, tumor necrosis factor (TNF), and interleukin-2 (IL-2) have been used in vaccine studies as a measurable immune parameter, reflecting activity of a vaccine and potentially predicting protection. However, accumulating experimental evidence suggests that host resistance against Mycobacterium tuberculosis infection is independent of IFN-γ and TNF secretion from CD4+ T cells. Furthermore, the booster vaccine MVA85A, despite generating a high level of multifunctional CD4+ T cell response in the host, failed to confer enhanced protection in vaccinated subjects. These findings suggest the need for identifying reliable correlates of protection to determine the efficacy of TB vaccine candidates. This article focuses on alternative pathways that mediate M. tuberculosis control and their potential for serving as markers of protection. The review also discusses the significance of investigating the natural human immune response to M. tuberculosis to identify the correlates of protection in vaccination.

Original languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalClinical and Vaccine Immunology
Issue number3
StatePublished - Mar 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)


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