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-γ 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-γ 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.
Hepatitis C virus polyprotien vaccine formulations capable of inducing broad antibody and cellular immune responses / M. Vadly, M. Selby, A. Medina Selby, D. Coit, J. Hall, L. Tandeske, D. Chien, C. Hu, D. Rosa, M. Singh, J. Kazzaz, S. Nguyen, S. Coates, P. Ng, S. Abrignani, Y. Lin, M. Houghton, D.T. O'Hagan. - In: JOURNAL OF GENERAL VIROLOGY. - ISSN 0022-1317. - 87:8(2006), pp. 2253-2262. [10.1099/vir.0.81849-0]
Hepatitis C virus polyprotien vaccine formulations capable of inducing broad antibody and cellular immune responses
S. Abrignani;
2006
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-γ 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-γ 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.File | Dimensione | Formato | |
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