Antigen-expressed recombinant Salmonella typhimurium driven by an in vivo-activated promoter is capable of inducing cellular immune response in transgenic mice.
To explore the approaches and mechanisms for reversing the immune tolerance in transgenic mouse, and the pathogenicity of hepatitis G virus (HGV), the promoter of phoP-activated gene (P(pagC)) of Salmonella typhimurium was used as a transcriptionally regulating element to construct an attenuated S. typhimurium expressing HGV NS3. The recombinant S. typhimurium was orally administered to HGV transgenic mice. As the results, HGV antigen in serum and liver as well as HGV mRNA in liver were decreased significantly, although the serum anti-HGV NS3 remained undetectable as the control transgenic mice. The spleen cell proliferation, in vitro HGV NS3 specific CTL, and IFN-gamma assays with the primed cultured splenocytes indicated the induction of Th1 immune responses in those administered transgenic mice. Adoptive transfer of fractionated primed spleen cells to the transgenic mice showed that T lymphocytes were responsible for, maybe through IFN-gamma, the down-regulation of HGV mRNA transcription. Histological examination found no significant inflammatory changes in liver of the transgenic mice. These findings suggested that the oral inoculation of the HGV NS3-expressed attenuated S. typhimurium driven by an in vivo-activated promoter should be a simple and effective approach for potential treatment of chronic viral infection.
Wang
Hong-Wei
HW
Department of Microbiology, Second Military Medical University, Shanghai 200433, China.
Zhang
Min
M
Luan
Jie
J
Hu
Wei-Jiang
WJ
Zhao
Ping
P
Gao
Jun
J
Qi
Zhong-Tian
ZT
D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D029407:GB virus C / Q000276:immunology*; D018963:Hepatitis Antigens / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D007167:Immunotherapy; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D020365:RNA Helicases; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics*; D012697:Serine Endopeptidases; D013601:T-Lymphocytes / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D016207:Cytokines; D018963:Hepatitis Antigens; D020365:RNA Helicases; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases