کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10968188 1102873 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A heat shock protein based polyvalent vaccine targeting HSV-2: CD4+ and CD8+ cellular immunity and protective efficacy
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
A heat shock protein based polyvalent vaccine targeting HSV-2: CD4+ and CD8+ cellular immunity and protective efficacy
چکیده انگلیسی
Efforts to develop a subunit vaccine against genital herpes have been hampered by lack of knowledge of the protective antigens of HSV-2, the causative agent of the disease. Vaccines based either on selected antigens or attenuated live virus approaches have not demonstrated meaningful clinical activity. We present here results of a therapeutic vaccine candidate, HerpV (formerly called AG-707), consisting of 32 HSV-2 peptides derived from 22 HSV-2 proteins, complexed non-covalently to the HSP70 chaperone and formulated with QS-21 saponin adjuvant. HerpV is observed to be immunogenic, generating CD4+ and CD8+ T cell responses in three mouse strains including HLA-A2 transgenic mice. Optimal T cell stimulation was dependent on the synergistic adjuvant properties of QS-21 with hsp70. The vaccine provided significant protection from viral challenge in a mouse prophylaxis model and showed signals of activity in a guinea pig therapeutic model of existing infection. Peripheral blood mononuclear cells from human HSV-2+ subjects also showed reactivity in vitro to a subset of individual peptides and to the pool of all 32 peptides. Recombinant human Hsc70 complexed with the 32 peptides also stimulated the expansion of CD8+ T cells from HSV-2+ subjects in vitro. These studies demonstrate that HerpV is a promising immunotherapy candidate for genital herpes, and provide a foundation for evaluating HerpV in human HSV-2+ subjects with the intent of eliciting CD4+ and CD8+ T cell responses to a broad array of viral antigens.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 29, Issue 47, 3 November 2011, Pages 8530-8541
نویسندگان
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