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Biotech / Medical : Indications -- Hepatitis -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (40)	5/14/2003 12:51:33 PM
From: tuck	Read Replies (1) \| Respond to of 312

[HCV -- Viral particle immunization] >>Published online before print May 14, 2003 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.1131929100 Medical Sciences Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection Kazumoto Murata , Martin Lechmann , Ming Qiao , Toshiaki Gunji , Harvey J. Alter , and T. Jake Liang * *Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, and Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892 Contributed by Harvey J. Alter, April 2, 2003 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.<< Cheers, Tuck