Recombinant M. smegmatis vaccine targeted delivering IL-12/GLS into macrophages can induce specific cellular immunity against M. tuberculosis in BALB/c mice.
In the present study, we constructed a viable therapeutic vaccine of recombinant M. smegmatis mediated IL-12/GLS (granulysin) gene transfer into murine macrophages to exert the immunotherapy effects on the Mycobacterium tuberculosis infection. We tested this recombinant therapeutic vaccine in an in vivo study to determine its capability of stimulating host specific immune responses against M. tuberculosis. BALB/c mice intranasally immunized with the therapeutic vaccine developed an efficient Th1 protective immune response against M. tuberculosis which was equal to that of the BCG strain. Inoculation intranasally with this viable vaccine induced high level of serum IFN-gamma, IL-12 and IgG2a. The viable vaccine was capable of inducing purified protein derivative (PPD) antigen-specific splenocytes proliferation and IFN-gamma production from T cells in spleens of the immunized mice. In addition, intranasally inoculation with the viable vaccine can induce PPD antigen-specific sIgA production in the broncho-alveolar lavage fluid (BALF) of the immunized mice. No change of IL-4 level was found in all groups. The therapeutic mechanism of this viable vaccine against M. tuberculosis infection observed here appeared to be a result of the specific Th1 immune response activated by mycobacterium antigen from M. smegmatis and the expression of sIL-12/GLS in alveolar macrophages via the M. smegmatis-mediated gene transfer method. This research demonstrates that the therapeutic gene can be introduced into a host by viable mycobacteria works to induce the host specific immune response against M. tuberculosis infection in vivo. Since this therapeutic vaccine can strongly induce specific Th1 responses against M. tuberculosis in BALB/c mice and has no obviously harmfulness to the host simultaneously, the recombinant vaccine might be a potential candidate therapeutic vaccine against tuberculosis.
Yi
Zhengjun
Z
Department of Immunology, Chongqing University of Medical Sciences, Chongqing 400016, China.
Fu
Yurong
Y
Yang
Chun
C
Li
Junming
J
Luo
Xudong
X
Chen
Quan
Q
Zeng
Wei
W
Jiang
Shan
S
Jiang
Ying
Y
He
Yonglin
Y
Yang
Jian
J
Liu
Yehua
Y
Li
Na
N
Zhu
Dao-Yin
DY
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; D018664:Interleukin-12