Enhanced cellular immunity to hepatitis C virus nonstructural proteins by codelivery of granulocyte macrophage-colony stimulating factor gene in intramuscular DNA immunization.
Hepatitis C virus (HCV) nonstructural (NS) proteins appeared to be important targets for HCV vaccine development, since NS-specific T-helper-cell responses are associated with clearance from acute HCV infection. In this report, we have constructed a plasmid, pTV-NS345, that encodes the HCV NS3, NS4 and NS5 proteins (NS345) and a bicistronic plasmid, PTV-NS345/GMCSF, in which the HCV NS345 polyprotein and GMCSF are translated independently. Intramuscular inoculation with pTV-NS345 plasmid DNA into the Buffalo rats generated both antibody and T-cell proliferative responses to each NS protein. The expression of GMCSF, together with HCV NS345 proteins, appeared to significantly increase T-cell proliferative responses. In particular, the inoculation of a bicistronic plasmid generated higher T-cell proliferative responses to each NS protein than did the coinjection of two separate plasmids, pTV-NS345 and pTV-GMCSF. These results demonstrate that the codelivery of GMCSF augmented HCV NS345-specific cellular immunity and that the intensity of the immunity was differed depending on how GMCSF gene is codelivered.
Cho
J H
JH
Department of Life Science, Center for Biofunctional Molecules, School of Environmental Engineering, Pohang University of Science and Technology, Kyungbuk, South Korea.
Lee
S W
SW
Sung
Y C
YC
D000818:Animals; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000096:biosynthesis; D007111:Immunity, Cellular; D007273:Injections, Intramuscular; D051381:Rats; D011915:Rats, Inbred BUF; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018937:Hepatitis C Antibodies; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase