Hepatitis C virus-like particles induce virus-specific humoral and cellular immune responses in mice.
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(H)1 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 3beta-[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.
Lechmann
M
M
Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Murata
K
K
Satoi
J
J
Vergalla
J
J
Baumert
T F
TF
Liang
T J
TJ
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation; D002784:Cholesterol / Q000031:analogs & derivatives / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D014771:Virion / Q000276:immunology*
D000276:Adjuvants, Immunologic; D009841:Oligonucleotides; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D002784:Cholesterol