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

• Published in: Biotechnology letters 2017-08, Vol.39 (8), p.1159-1166
• Main Authors: Sun, Li, Yuan, Quan, Xu, Tianhua, Yao, Li, Feng, Jiangmin, Ma, Jianfei, Wang, Lining, Lv, Changlong, Wang, Danan
• Format: Article
• Language: English
• Subjects: Acyltransferases - chemistry; Acyltransferases - genetics; Acyltransferases - immunology; Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - genetics; Animals; Antigens; Antigens, Bacterial - chemistry; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Applied Microbiology; Biochemistry; Biomedical and Life Sciences; Biotechnology; Bronchoalveolar Lavage Fluid - cytology; CD4 antigen; CD8 antigen; Cell proliferation; Cells, Cultured; Cloning, Molecular; Cytokines; Deoxyribonucleic acid; DNA; DNA vaccines; Fusion protein; HEK293 Cells; Humans; Immune response; Immunization; Immunoglobulin A; Immunoglobulin G; Interferon; Interferon-gamma - chemistry; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin 15; Life Sciences; Lungs; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Microbiology; Natural killer cells; Original Research Paper; Plasmids; Polarization; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Rodents; Spleen; Spleen - cytology; Tuberculosis; Tuberculosis Vaccines - chemistry; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Vaccination; Vaccines; Vaccines, DNA - chemistry; Vaccines, DNA - genetics; Vaccines, DNA - immunology; γ-Interferon
• ISSN: 0141-5492; 1573-6776
• DOI: 10.1007/s10529-017-2342-1

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.