title: Hepatitis C virus polyprotein vaccine formulations capable of inducing broad antibody and cellular immune responses.
abstract: Although approximately 3 % of the world's population is infected with Hepatitis C virus (HCV), there is no prophylactic vaccine available. This study reports the design, cloning and purification of a single polyprotein comprising the HCV core protein and non-structural proteins NS3, NS4a, NS4b, NS5a and NS5b. The immunogenicity of this polyprotein, which was formulated in alum, oil-in-water emulsion MF59 or poly(dl-lactide co-glycolide) in the presence or absence of CpG adjuvant, was then determined in a murine model for induction of B- and T-cell responses. The addition of adjuvants or a delivery system to the HCV polyprotein enhanced serum antibody and T-cell proliferative responses, as well as IFN-gamma responses, by CD4+ T cells. The antibody responses were mainly against the NS3 and NS5 components of the polyprotein and relatively poor responses were elicited against NS4 and the core components. IFN-gamma responses, however, were induced against all of the individual components of the polyprotein. These data suggest that the HCV polyprotein delivered with adjuvants induces broad B- and T-cell responses and could be a vaccine candidate against HCV.
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Vajdy
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Selby
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Angelica
authors.initials: A
authors.lastname: Medina-Selby
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Doris
authors.initials: D
authors.lastname: Coit
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hall
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Tandeske
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chien
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Celine
authors.initials: C
authors.lastname: Hu
authors.affiliation: Chiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Rosa
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Jina
authors.initials: J
authors.lastname: Kazzaz
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Coates
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Ng
authors.affiliation: Chiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Yin-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Houghton
authors.affiliation: Chiron Vaccines, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology; D011098:Polyglactin 910 / Q000008:administration & dosage; D020815:Polyproteins / Q000235:genetics / Q000276:immunology*; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; C089950:MF59 oil emulsion; D009838:Oligodeoxyribonucleotides; D020815:Polyproteins; D011136:Polysorbates; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D011098:Polyglactin 910; C041524:aluminum sulfate; D013185:Squalene; D007371:Interferon-gamma