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Clin Vaccine Immunol. 2015 Mar;22(3):258-66. doi: 10.1128/CVI.00721-14. Epub 2015 Jan 14.

Quest for correlates of protection against tuberculosis.

Author information

1
Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.
2
Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA.
3
Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA salgampa@njms.rutgers.edu.

Abstract

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.

PMID:
25589549
PMCID:
PMC4340894
DOI:
10.1128/CVI.00721-14
[Indexed for MEDLINE]
Free PMC Article

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