Hepatitis C Virus-Like Particles Induce Virus–Specific Humoral and Cellular Immune Responses in Mice

Abstract

We have recently described the production of hepatitis C virus-like particles (HCV–LPs) in insect cells that resemble the putative virions. Here we evaluate the humoral and cellular immunogenicity of the virus–like particles with or without viral p7 protein, a small viral polypeptide that resides between the structural and nonstructural regions of the HCV polyprotein and whose function has not been defined. Immunized BALB/c mice developed high titers of anti–E2 antibodies and virus–specific cellular immune responses including cytotoxic T lymphocytes and T helper responses with gamma interferon production. The virus–like particles without p7 generated a higher cellular immune response with a more T_H1 profile than the particles with p7. Immunization of heat–denatured particles resulted in substantially lower humoral and cellular responses, suggesting that the immunogenicity is strongly dependent on particle formation. Administration of CpG oligonucleotide or cationic lipid 3β–[N–(N',N'–dimethylaminoethane)carbamoyl]cholesterol (DC–Chol), two potent adjuvants, did not significantly enhance the immunogenicity of HCV–LPs. Our results indicate that HCV–LPs can induce humoral and cellular immune responses and offer a promising approach to vaccine development.