Identification of CD4+ and CD8+ T cell epitopes of woodchuck hepatitis virus core and surface antigens in BALB/c mice

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• 作者：L. Ochoa-Callejero ; I. Otano ; A. Vales ; C. Olagü ; e ; P. Sarobe ; J.J. Lasarte ; J. Prieto ; S. Menne ; G. Gonzá ; lez-Aseguinolaza
• 关键词：Woodchuck hepatitis virus ; T cell epitopes ; Hepatitis B virus ; Chronic hepatitis infection ; DNA vaccine
• 刊名：Vaccine
• 出版年：2010
• 出版时间：19 July 2010
• 年：2010
• 卷：28
• 期：32
• 页码：5323-5331
• 全文大小：284 K

文摘

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-2^d-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-2^d 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.