Efficient induction of mouse immune responses to hepatitis C virus by viral core protein-carrying attenuated Salmonella typhimurium.
Hepatitis C virus (HCV) core protein is considered to be an attractive candidate for inclusion in a protective vaccine. However, this protein may attenuate the development of systemic immune responses because of its immunomodulatory properties. In this study, a eukaryotic expression plasmid, pCI-C, and an in vivo-inducible prokaryotic expression plasmid, pZW-C, for HCV core protein were constructed and transformed into attenuated Salmonella typhimurium aroA strain SL7207. The recombinant expression plasmids SL7207/pCI-C and SL7207/pZW-C were used to orally immunize BALB/c mice, and immune responses specific to core protein were assessed. Immunization with bacteria SL7207/pCI-C led to a persistent decrease in the percentage of CD3(+)CD4(+) T cells and triggered weak anti-core IgG production. Splenocytes from SL7207/pCIC-immunized mice developed relatively weak proliferation response, low interferon-gamma secretion, and inferior cytotoxic activity compared with those from mice immunized with SL7207/pZW-C. Boost immunization with SL7207/pCI-C yielded limited improvement in the immune response, whereas boost with bacteria SL7207/pZW-C enhanced immune responses significantly. These results suggest that de novo host synthesis of native HCV core protein may cut down the induction of immune responses. Attenuated S. typhimurium carrying HCV core protein could efficiently activate systemic cellular and humoral responses, and may be a promising strategy for the development of core-based HCV vaccines.
Liao
Xiao-Ling
XL
Department of Microbiology, State Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, People's Republic of China.
Ren
Hao
H
Zhao
Ping
P
Zhu
Shi-Ying
SY
Cao
Jie
J
Chen
Zhi-Hui
ZH
Zhao
Lan-Juan
LJ
Pan
Wei
W
Feitelson
Mark Alan
MA
Qui
Zhong-Tian
ZT
D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*
D001428:Bacterial Vaccines; D018937:Hepatitis C Antibodies; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines; C069130:nucleocapsid protein, Hepatitis C virus