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Enhanced hepatitis C virus NS3 specific Th1 immune responses induced by co-delivery of protein antigen and CpG with cationic liposomes

Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, Building 10, Room 1C711, National Institutes of Health, Bethesda, MD 20892-1184, USA

Correspondence
J. Wai-Kuo Shih
jshih{at}mail.cc.nih.gov

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.

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