Enhanced hepatitis C virus NS3 specific Th1 immune responses induced by co-delivery of protein antigen and CpG with cationic liposomes.
Mice were immunized intramuscularly with free recombinant hepatitis C virus (HCV) NS3 (non-structural protein 3) protein, liposomes encapsulating rNS3 or rNS3 and CpG mixture, liposomes co-encapsulating rNS3 and CpG or liposomes co-encapsulating rNS3 and GpC. Liposomes co-encapsulating rNS3 and CpG induced a much higher titre of anti-HCV NS3 IgG and the dominant IgG subtype was IgG2a. Liposomes co-encapsulating rNS3 and GpC also induced high levels of anti-HCV NS3 IgG antibody, but the dominant IgG subtype was still IgG1, the same as in free HCV/NS3 immunized mice. Liposomes encapsulating rHCV NS3 and the mixture of rHCV NS3 and CpG did not increase the antibody response but switched the IgG subtype. A cytokine profile analysis revealed that the levels of Th1 cytokines in the mice immunized with liposomes co-encapsulating rHCV NS3 and CpG were significantly higher than in other mice while the levels of Th2 cytokine were significantly lower than in the mice immunized with naked rNS3. IL-12 in the mice immunized with liposome-NS3-CpG was significantly higher than in other mice. In conclusion, liposomes co-encapsulating HCV NS3 and CpG are a good candidate vaccine to induce strong Th1 immune responses against hepatitis C viruses.
Jiao
Xuanmao
X
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, Building 10, Room 1C711, National Institutes of Health, Bethesda, MD 20892-1184, USA.
Wang
Richard Yan-Hui
RY
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, Building 10, Room 1C711, National Institutes of Health, Bethesda, MD 20892-1184, USA.
Qiu
Qi
Q
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, Building 10, Room 1C711, National Institutes of Health, Bethesda, MD 20892-1184, USA.
Alter
Harvey J
HJ
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, Building 10, Room 1C711, National Institutes of Health, Bethesda, MD 20892-1184, USA.
Shih
J Wai-Kuo
JW
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, Building 10, Room 1C711, National Institutes of Health, Bethesda, MD 20892-1184, USA.
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; 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
D016207:Cytokines; D018937:Hepatitis C Antibodies; D007074:Immunoglobulin G; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C408982:CPG-oligonucleotide; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases