Vaccine-induced Anti-Tuberculosis Protective Immunity in Mice Correlates With the Magnitude and Quality of Multifunctional CD4 T Cells

Vaccine. 2011 Apr 5;29(16):2902-9. doi: 10.1016/j.vaccine.2011.02.010. Epub 2011 Feb 21.

Abstract

The development of improved vaccines against Mycobacterium tuberculosis has been hindered by a limited understanding of the immune correlates of anti-tuberculosis protective immunity. In this study, we examined the relationship between long-term anti-tuberculosis protection and the mycobacterial-specific CD4 multifunctional T (MFT) cell responses induced by five different TB vaccines (live-attenuated, subunit, viral vectored, plasmid DNA, and combination vaccines) in a mouse model of pulmonary tuberculosis. In a 14-month experiment, we showed that TB vaccine-induced CD4 T cell responses were heterogenous. Antigen-specific monofunctional CD4 T cells expressing single cytokines and MFT CD4 T cells expressing multiple cytokines (IFN-γ and TNF-α, IFN-γ and IFN-γ, TNF-α, and IL-2, and all three cytokines) were identified after the immunizations. Interestingly, compared to the monofunctional cells, significantly higher median fluorescent intensities (MFIs) for IFN-γ and TNF-α were detected for triple-positive MFT CD4 T cells induced by the most protective vaccines while modest differences in relative MFI values were seen for the less protective preparations. Most importantly during the 14-month study, the levels of vaccine-induced pulmonary and splenic protective immunity correlated with the frequency and the integrated MFI (iMFI, frequency×MFI) values of triple-positive CD4 T cells that were induced by the same vaccines. These data support efforts to use MFT cell analyses as a measure of TB vaccine immunogenicity in human immunization studies.

Publication types

  • Comparative Study

MeSH terms

  • Acyltransferases / immunology
  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / immunology
  • Female
  • Immunity, Cellular*
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology
  • Tuberculosis Vaccines / immunology*
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / prevention & control
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Tuberculosis Vaccines
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis