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

Gastroenterology. 1999 Dec;117(6):1397-407. doi: 10.1016/s0016-5085(99)70290-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Glycosylation
  • Hepacivirus / genetics*
  • Hepacivirus / immunology
  • Hepacivirus / metabolism
  • Insecta
  • Vaccines, Synthetic / genetics*
  • Viral Envelope Proteins / analysis
  • Viral Hepatitis Vaccines / genetics*
  • Viral Structural Proteins / analysis
  • Virus Replication

Substances

  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines
  • Viral Structural Proteins