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Journal of Virology, July 2004, p. 6995-7003, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6995-7003.2004

Immunization with Hepatitis C Virus-Like Particles Induces Humoral and Cellular Immune Responses in Nonhuman Primates

Sook-Hyang Jeong ,1,{dagger},{ddagger} Ming Qiao,1,{dagger},§ Michelina Nascimbeni,1 Zongyi Hu,1 Barbara Rehermann,1 Krishna Murthy,2 and T. Jake Liang1*

Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas, 782272

Received 20 November 2003/ Accepted 19 February 2004

We have previously reported the production of hepatitis C virus-like particles (HCV-LP) using a recombinant baculovirus containing the cDNA of the HCV structural proteins (core, E1, and E2). These particles resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice. Here we present evidence on the immunogenicity of HCV-LP and the effects of novel adjuvant systems in a nonhuman primate model, the baboon. Three groups of four baboons were immunized with HCV-LP, HCV-LP and adjuvant AS01B (monophosphoryl lipid A and QS21), or HCV-LP and the combination of AS01B and CpG oligodeoxynucleotides 10105. After four immunizations over an 8-month period, all animals developed HCV-specific humoral and cellular immune responses including antibodies to HCV structural proteins and gamma interferon+ (IFN-{gamma}+)CD4+ and IFN-{gamma}+CD8+ T-cell responses. The immunogenicity of HCV-LP was only marginally enhanced by the use of adjuvants. The overall HCV-specific immune responses were broad and long lasting. Our results suggest that HCV-LP is a potent immunogen to induce HCV-specific humoral and cellular immune responses in primates and may be a promising approach to develop novel preventive and therapeutic modalities.

* Corresponding author. Mailing address: Liver Disease Section, NIDDK, National Institutes of Health, 10 Center Dr., Room 9B16, Bethesda, MD 20892-1800. Phone: (301) 496-1721. Fax: (301) 402-0491. E-mail: jliang{at}nih.gov.

{dagger} S.-H.J. and M.Q. contributed equally to this work.

{ddagger} Present address: Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.

§ Present address: Infectious Diseases Division, Institute of Medical and Veterinary Science, Adelaide, South Australia 5000, Australia.

Journal of Virology, July 2004, p. 6995-7003, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6995-7003.2004




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