کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2409858 1103235 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel vaccines for the treatment of chronic HBV infection based on mycobacterial heat shock protein 70
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Novel vaccines for the treatment of chronic HBV infection based on mycobacterial heat shock protein 70
چکیده انگلیسی

Immunogenic peptide-based vaccines can raise significant cellular immune responses. Although cytotoxic T lymphocytes (CTL) peptide epitopes are generally poor immunogens, heat shock protein 70 from Mycobacterium tuberculosis (TBhsp70) can overcome this problem since it is a potent adjuvant that links innate and adaptive immune responses. Our goal is to use TBhsp70 as an adjuvant for development of therapeutic vaccines for chronic Hepatitis B virus infection (HBV). To this end, we genetically fused the HBV core 18–27 peptide (HBcAg(18–27)) as a CTL epitope to the C-terminus of TBhsp70 and expressed the resulting protein in methylotropic yeast Pichia pastoris GS115. At the same time, the TBhsp70-HBcAg(18–27) peptide complex was reconstituted in vitro. We investigated whether TBhsp70–peptide complex and TBhsp70–peptide fusion protein could generate antigen specific CTL responses in vitro. Dendritic cells (DC) from HLA-A2+ chronic HBV infection and healthy control pulsed with two vaccines were studied phenotypically by FACS analyses and functionally by cytokine release, and HBV-specific CTL response. Our results demonstrate that two vaccines can activate DC of chronic HBV infection and healthy control by upregulation CD40 and CD86, high production of IL-12p70 and TNF-α. Furthermore, autologous T cells with DC stimulated by two vaccines can produce IFN-γ and generate HBV-specific CTL response. However, capacity for CTL response and cytokines production from HBV infections remained inferior to that of healthy controls. Thus, the strategy of utilizing TBhsp70 may provide a novel design for the development of prophylactic and therapeutic vaccines.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 24, Issue 7, 13 February 2006, Pages 887–896
نویسندگان
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