کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3431439 1594409 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Improving recombinant MVA immune responses: Potentiation of the immune responses to HIV-1 with MVA and DNA vectors expressing Env and the cytokines IL-12 and IFN-gamma
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Improving recombinant MVA immune responses: Potentiation of the immune responses to HIV-1 with MVA and DNA vectors expressing Env and the cytokines IL-12 and IFN-gamma
چکیده انگلیسی

Recombinants based on vaccinia virus vectors, especially on the highly attenuated modified vaccinia virus Ankara (MVA) strain, are now being tested in clinical trials for safety and immunogenicity, using prime/boost heterologous regimes of vaccination. Due to the limited replication capacity of MVA, it is necessary to develop procedures that can enhance the specific cellular immune responses to the recombinant antigen delivered by the MVA vector. In this investigation, we have characterized the systemic immune responses in BALB/c mice using interferon-gamma (IFN-γ) or interleukin-12 (IL-12) in an adjuvant-like manner elicited by MVA recombinants or naked DNA vectors expressing one of those cytokines in combination with the human immunodeficiency virus type 1 (HIV-1) envelope (Env) as antigen. In infected mice, virus gene expression in splenocytes and levels of cytokines IFN-γ and IL-12 in serum were maximal by 6 h post-infection (hpi) with MVA recombinants expressing IFN-γ (MVAIFN-γ) or IL-12 (MVAIL-12). In the infected animals, co-expression of HIV-1 env (MVAENV) and either IFN-γ or IL-12 from MVA recombinants produced a two and three-fold increase of anti-env CD8+ T cell response, respectively. When priming was carried out with DNA vectors expressing HIV-1 env and either IFN-γ or IL-12, the magnitude of the specific anti-env CD8+ T cell stimulation after MVAENV booster was further enhanced. Our findings revealed that IFN-γ or IL-12 can be used to potentiate the cellular immune response to HIV-1 env, when delivered either from a single MVA recombinant or from a DNA vector. The increment of the CD8+ T cell response was higher in a DNA/MVA prime/boost protocol. Thus, the immune response of MVA vectors can be improved with the co-delivery of the cytokines IFN-γ or IL-12.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virus Research - Volume 116, Issues 1–2, March 2006, Pages 11–20
نویسندگان
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