BACKGROUND & AIMS: Plasmid DNA-based immunization has been shown to be an effective means of vaccination in animal models. In this study, the immune responses to various hepatitis C virus structural protein antigens were evaluated using this technique. METHODS: Six recombinant plasmids were constructed. These include, individually, the coding regions for the core protein (pC); E1 (pE1) and E2 (pE2); as well as core, E1, and E2 together (pCE1E2); E1 and E2 together (pE1E2); and finally an E2 construct from which the N-terminal hypervariable region had been deleted (pE2 deltaHVR). These plasmids were transfected into mammalian cells to test their protein expression and were injected into the quadriceps muscles of BALB/c mice to measure specific antibodies and cytotoxic T-lymphocyte responses. RESULTS: All the recombinant plasmids were shown to express specific antigens transiently in cells and elicited specific antibody responses to core, E1, and E2 in mice. Specific cytotoxic T lymphocyte responses were detected only in mice injected with plasmid constructs encoding the core. CONCLUSIONS: Genetic immunization can aid the development of hepatitis C virus vaccines by allowing for the rapid construction and evaluation of different expression plasmids as potential immunogens.
BACKGROUND & AIMS: Plasmid DNA-based immunization has been shown to be an effective means of vaccination in animal models. In this study, the immune responses to various hepatitis C virus structural protein antigens were evaluated using this technique. METHODS: Six recombinant plasmids were constructed. These include, individually, the coding regions for the core protein (pC); E1 (pE1) and E2 (pE2); as well as core, E1, and E2 together (pCE1E2); E1 and E2 together (pE1E2); and finally an E2 construct from which the N-terminal hypervariable region had been deleted (pE2 deltaHVR). These plasmids were transfected into mammalian cells to test their protein expression and were injected into the quadriceps muscles of BALB/c mice to measure specific antibodies and cytotoxic T-lymphocyte responses. RESULTS: All the recombinant plasmids were shown to express specific antigens transiently in cells and elicited specific antibody responses to core, E1, and E2 in mice. Specific cytotoxic T lymphocyte responses were detected only in mice injected with plasmid constructs encoding the core. CONCLUSIONS: Genetic immunization can aid the development of hepatitis C virus vaccines by allowing for the rapid construction and evaluation of different expression plasmids as potential immunogens.
Authors: T Arichi; T Saito; M E Major; I M Belyakov; M Shirai; V H Engelhard; S M Feinstone; J A Berzofsky Journal: Proc Natl Acad Sci U S A Date: 2000-01-04 Impact factor: 11.205
Authors: M E Major; K Mihalik; J Fernandez; J Seidman; D Kleiner; A A Kolykhalov; C M Rice; S M Feinstone Journal: J Virol Date: 1999-04 Impact factor: 5.103
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Authors: Benjamin E Simon; Kenneth A Cornell; Tina R Clark; Sunwen Chou; Hugo R Rosen; Ronald A Barry Journal: Infect Immun Date: 2003-11 Impact factor: 3.441