Novel adjuvant for immunization against tuberculosis: DNA vaccine expressing Mycobacterium tuberculosis antigen 85A and interleukin-15 fusion product elicits strong immune responses in mice

Biotechnol Lett. 2017 Aug;39(8):1159-1166. doi: 10.1007/s10529-017-2342-1. Epub 2017 May 3.

Abstract

Objectives: To investigate the potential of interleukin (IL)-15 as a novel adjuvant for Mycobacterium tuberculosis (Mtb) antigen 85A (Ag85A) vaccine.

Results: C57BL/6 mice were intramuscularly immunized three times with a plasmid expressing the Ag85A-IL-15 fusion protein (pcDNA3.1-Ag85A-IL-15), with the empty pcDNA3.1 vector and the pcDNA3.1-Ag85A as control. Mice vaccinated with pcDNA3.1-Ag85A-IL-15 generated more secretory IgA (sIgA) into their lung (209 ± 21 μg/ml) and acquired an enhanced serum IgG response to Ag85A. IgG2a/IgG1 ratios were upregulated, natural killer cell activity was augmented and Ag85A-specific splenic T cell proliferation was enhanced in these mice as well. Vaccination with pcDNA3.1-Ag85A-IL-15 promoted the polarization of CD4+ T cells towards a Th1 type in the spleen, and significantly upregulated the serum level of interferon (IFN)-γ (458 ± 98 pg/ml), a typical Th1 cytokine. IFN-γ-expressing CD8+ cells were also increased in the spleen after pcDNA3.1-Ag85A-IL-15 immunization.

Conclusions: A superior immune type I response in mice vaccinated with plasmid Ag85A-IL-15 has been achieved.

Keywords: Antigen Ag85A; IgG; Interferon-γ; Interleukin-15; Mycobacterium tuberulosis; Novel adjuvant; Th1 cells.

MeSH terms

  • Acyltransferases / chemistry
  • Acyltransferases / genetics
  • Acyltransferases / immunology*
  • Adjuvants, Immunologic* / chemistry
  • Adjuvants, Immunologic* / genetics
  • Animals
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Cells, Cultured
  • Cloning, Molecular
  • HEK293 Cells
  • Humans
  • Interferon-gamma / chemistry
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Plasmids
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Spleen / cytology
  • Tuberculosis
  • Tuberculosis Vaccines / chemistry
  • Tuberculosis Vaccines / genetics
  • Tuberculosis Vaccines / immunology*
  • Vaccines, DNA / chemistry
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Recombinant Fusion Proteins
  • Tuberculosis Vaccines
  • Vaccines, DNA
  • Interferon-gamma
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis