Effect of hsp65 DNA vaccination carrying immunostimulatory DNA sequences (CpG motifs) against Mycobacterium leprae multiplication in mice.
A DNA expressing hsp65 of Mycobacterium leprae (pACB/hsp65) was constructed by using a vector containing immunostimulatory DNA sequences (pACB). At 12 weeks post-immunization, spleen cells from BALB/cA mice immunized with pACB/hsp65, produced a significantly higher amount of IFN-gamma than mice immunized with pACB in the absence of any in vitro stimulation, and further enhanced its production upon secondary in vitro stimulation with M. leprae lysate and hsp65. On the other hand, while production of IL-12 was observed in mice immunized with pACB/hsp65 12 weeks before, the cytokine production was inhibited by in vitro secondary stimulation with M. leprae or hsp65. At 18 weeks post-immunization, the production of both IFN-gamma and IL-12 was apparently down-regulated, but that of IL-10 was up-regulated. IL-10 seemed to suppress the IFN-gamma and IL-12 productions, because their production was recovered by neutralization of IL-10 with anti-IL-10 mAb. Furthermore, when the efficiency of pACB/hsp65 as a vaccine against M. leprae was evaluated in vivo, the mice immunized with pACB/hsp65 suppressed the multiplication of subsequently challenged M. leprae. These results suggest that a DNA containing M. leprae-derived hsp65 and immunostimulatory sequences might be a potent vaccine candidate against M. leprae infection.
Nomaguchi
Hiroko
H
Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1-Aobacho, Higashimurayama, Tokyo, Japan.
Mukai
Tetsu
T
Takeshita
Fumihiko
F
Matsuoka
Masanori
M
Maeda
Yumi
Y
Aye
Tin Maung
TM
Jahan
Nilufar
N
Yogi
Yasuko
Y
Endo
Masumi
M
Sato
Yukio
Y
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D018899:CpG Islands / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007114:Immunization; D007918:Leprosy / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009166:Mycobacterium leprae / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms; D019444:Vaccines, DNA / Q000276:immunology*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D018834:Chaperonin 60; D016207:Cytokines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D009569:Nitric Oxide; D018833:Chaperonins