Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection.
We have recently demonstrated that immunization with hepatitis C virus-like particles (HCV-LPs) generated in insect cells can elicit both humoral and cellular immune responses in BALB/c mice. Here, we evaluate the immunogenicity of HCV-LPs in HLA2.1 transgenic (AAD) mice in comparison to DNA immunization. HCV-LP immunization elicited a significantly stronger humoral immune response than DNA immunization. HCV-LP-immunized mice also developed stronger HCV-specific cellular immune responses than DNA-immunized mice as determined by using quantitative enzyme-linked immunospot (ELISpot) assay and intracellular cytokine staining. In BALB/c mice, immunization with HCV-LPs resulted in a >5 log10 reduction in vaccinia titer when challenged with a recombinant vaccinia expressing the HCV structural proteins (vvHCV.S), as compared to 1 log10 decrease in DNA immunization. In HLA2.1 transgenic mice, a 1-2 log10 reduction resulted from HCV-LP immunization, whereas no reduction was seen from DNA immunization. Adoptive transfer of lymphocytes from HCV-LP-immunized mice to naive mice provided protection against vvHCV.S challenge, and this transferred immunity can be abrogated by either CD4 or CD8 depletion. Our results suggest that HCV-LPs can induce humoral and cellular immune responses that are protective in a surrogate HCV challenge model and that a strong cellular immunity provided by both CD4 and CD8 effector lymphocytes may be important for protection from HCV infection.
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kazumoto
K
Murata
Martin
M
Lechmann
Ming
M
Qiao
Toshiaki
T
Gunji
Harvey J
HJ
Alter
T Jake
TJ
Liang
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D014615:Vaccinia / Q000517:prevention & control*; D014616:Vaccinia virus / Q000235:genetics*