DNA vaccine using hemagglutinating virus of Japan-liposome encapsulating combination encoding mycobacterial heat shock protein 65 and interleukin-12 confers protection against Mycobacterium tuberculosis by T cell activation.
We investigated the immunogenicity and protective efficacy of DNA vaccine combinations expressing mycobacterial heat shock protein 65 (Hsp65) and interleukin-12 (IL-12) using gene gun bombardment and the hemagglutinating virus of Japan (HVJ)-liposome method. A mouse IL-12 expression vector (mIL-12 DNA) encoding single-chain IL-12 proteins comprised of p40 and p35 subunits were constructed. In a mouse model, a single gene gun vaccination with the combination of Hsp65 DNA and mIL-12 DNA provided a remarkably high degree of protection against challenge with virulent Mycobacterium tuberculosis; bacterial numbers were 100-fold lower in the lungs compared to BCG-vaccinated mice. To explore the clinical use of the DNA vaccines, we evaluated HVJ-liposome encapsulated Hsp65 DNA and mIL-12DNA (Hsp65 + mIL-12/HVJ). The HVJ-liposome method improved the protective efficacy of the Hsp65 DNA vaccine compared to gene gun vaccination. Hsp65 + mIL-12/HVJ induced CD8+ cytotoxic T lymphocyte activity against Hsp65 antigen. Most importantly, Hsp65+mIL-12/HVJ vaccination resulted in a greater degree of protection than that evoked by BCG. This protective efficacy was associated with the emergence of IFN-gamma-secreting T cells and activation of proliferative T cells and cytokines (IFN-gamma and IL-2) production upon stimulation with Hsp65 and antigens from M. tuberculosis. These results suggest that Hsp65 + IL-12/HVJ could be a promising candidate for a new tuberculosis DNA vaccine, which is superior to BCG vaccine.
Yoshida
Shigeto
S
Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical School, Tochigi 329-0498, Japan. shigeto@jichi.ac.jp
Tanaka
Takao
T
Kita
Yoko
Y
Kuwayama
Sachiko
S
Kanamaru
Noriko
N
Muraki
Yumiko
Y
Hashimoto
Satomi
S
Inoue
Yoshikazu
Y
Sakatani
Mitsunori
M
Kobayashi
Eiji
E
Kaneda
Yasufumi
Y
Okada
Masaji
M
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D019470:Biolistics; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics* / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D008081:Liposomes; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D029082:Sendai virus / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D001426:Bacterial Proteins; D018834:Chaperonin 60; D008081:Liposomes; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12; D007371:Interferon-gamma; D018833:Chaperonins