Identification of CD4+ and CD8+ T cell epitopes of woodchuck hepatitis virus core and surface antigens in BALB/c mice |
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Authors: | L. Ochoa-Callejero,I. Otano,A. Vales,C. Olagü e,P. Sarobe,J.J. Lasarte,J. Prieto,S. Menne,G. Gonzá lez-Aseguinolaza |
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Affiliation: | 1. Laboratory of Gene Therapy of Viral Hepatitis, Division of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA), Pamplona, Navarra, Spain;2. Department of Clinical Sciences, Gastrointestinal Unit, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA |
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Abstract: | A therapeutic vaccine against chronic hepatitis B virus (HBV) infection requires the development of a strong and multispecific Th1 cell immune response. Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) closely resemble HBV infection and represent the best animal model for this hepadnavirus-induced disease. Using the BIMAS “HLA Peptide Binding Predictions” program, we have identified and further characterized novel H-2d-restricted CD8+ epitopes within the WHV core (peptides C#12–21, C#18–32, C#19–27, C#61–69) and surface antigens (peptides preS2#10–18, preS2#27–35, S#76–84, S#133–140 and S#257–265), respectively. These peptides bind to H-2d with high efficiency and upon immunization of mice with peptide and Freund's adjuvant they induce the development of IFN-γ producing T cells. More importantly, WHV core peptides C#19–27 and C#61–69 and WHV surface peptides S#133–140 and S#257–265 were also recognized by CD8+ T cells after immunization of mice with DNA/PEI nanoparticles. Direct stimulation of splenocytes obtained from such DNA-immunized mice with peptides C#18–32, S#76–84, and S#257–265 resulted in significant production of IFN-γ. Thus, we have identified T cell determinants in mice from WHV core and surface antigens that have important value for designing and evaluating an effective vaccine against hepadnavirus infection. |
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Keywords: | WHV, woodchuck hepatitis virus WHcAg, woodchuck hepatitis core antigen WHpreS2-S, WHV surface antigen covering the preS2 and S regions PEI, polyethylenimine |
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