Hepatitis C virus-like particles synthesized in insect cells as a potential vaccine candidate

被引:104
作者
Baumert, TF
Vergalla, J
Satoi, J
Thomson, M
Lechmann, M
Herion, D
Greenberg, HB
Ito, S
Liang, TJ
机构
[1] NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA
[2] Stanford Univ, Sch Med, Div Gastroenterol, Palo Alto, CA 94304 USA
[3] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
关键词
D O I
10.1016/S0016-5085(99)70290-8
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. Successful vaccine development is crucial in controlling global HCV infection. We have previously described the generation of HCV-like particles (HCV-LPs) in insect cells using a recombinant baculovirus containing the complementary DNA of the HCV structural proteins. These HCV-LPs had similar morphological and biophysical properties as the putative virions. In this study, we analyzed the structural features, antigenic composition, seroreactivity, and immunogenicity of purified HCV-LPs. Methods: HCV-LPs were analyzed by electron microscopy and antibody immunolabeling and precipitation, An enzyme-linked immunosorbent assay (ELISA) using HCV-LPs was developed. The humoral response to HCV-LPs in mice was studies by core and envelope ELISAs, Western immunoblotting, and immunofluorescence. Results: Structural and antigenic compositions of HCV-LPs were shown to be similar to those of putative HCV virions. Using the HCV-LP ELISA, high-titer anti-HCV antibodies were detected in individuals infected with various HCV genotypes, In vivo, HCV-LPs elicited a humoral response broadly directed against HCV structural proteins, Conclusions: HCV-LPs resemble HCV virions and are capable of inducing a humoral response targeted against various regions of HCV structural proteins, suggesting that HCV-LPs may be promising as a potential vaccine candidate.
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页码:1397 / 1407
页数:11
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