Alarmin IL-33 elicits potent TB-specific cell-mediated responses

Hum Vaccin Immunother. 2015;11(8):1954-60. doi: 10.1080/21645515.2015.1026499.

Abstract

Tuberculosis (TB) still remains a major public health issue despite the current available vaccine for TB, Bacille Calmette Guerin (BCG). An effective vaccine against TB remains a top priority in the fight against this pandemic bacterial infection. Adequate protection against TB is associated with the development of TH1-type and CD8(+) T cell responses. One alarmin cytokine, interleukin 33 (IL-33), has now been implicated in the development of both CD4(+) TH1 and CD8(+) T cell immunity. In this study, we determined whether the administration of IL-33 as an adjuvant, encoded in a DNA plasmid, could enhance the immunogenicity of a TB DNA vaccine. We report that the co-immunization of IL-33 with a DNA vaccine expressing the Mycobacterium Tuberculosis (Mtb) antigen 85B (Ag85B) induced robust Ag85B-specific IFNγ responses by ELISpot compared to Ag85B alone. Furthermore, these enhanced responses were characterized by higher frequencies of Ag85B-specific, multifunctional CD4(+) and CD8(+) T cells. Vaccination with IL-33 also increased the ability of the Ag85B-specific CD8(+) T cells to undergo degranulation and to secrete IFNγ and TNFα cytokines. These finding highlights IL-33 as a promising adjuvant to significantly improve the immunogenicity of TB DNA vaccines and support further study of this effective vaccine strategy against TB.

Keywords: DNA vaccines; Interleukin 33; TB vaccines; adjuvants; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology*
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / metabolism*
  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Enzyme-Linked Immunospot Assay
  • Female
  • Interferon-gamma / metabolism
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism*
  • Mice, Inbred C57BL
  • Th1 Cells / immunology*
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / genetics
  • Tuberculosis Vaccines / immunology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Bacterial Proteins
  • Interleukin-33
  • Tuberculosis Vaccines
  • Tumor Necrosis Factor-alpha
  • Vaccines, DNA
  • Interferon-gamma
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis