کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10964891 | 1102729 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel challenge model to evaluate the efficacy of hepatitis C virus vaccines in mice
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کلمات کلیدی
DAASVRFMDVNaBSEAPEMCV IRESα-fetoprotein - α-فتو پروتئینSecreted alkaline phosphatase - آلکالن فسفاتاز تثبیت شدهNeutralizing antibody - آنتی بادی غیرطبیعیifu - اگرPlis - بیشترHydrodynamic injection - تزریق هیدرودینامیکAFP - تست AFP یا آلفا فیتو پروتئینAnimal models - مدل های حیوانیHepatitis C virus - هپاتیت سیinfectious units - واحدهای عفونیVaccine - واکسنFoot and mouth disease virus - ویروس بیماری پا و دهانrecombinant vaccinia virus - ویروس واکسیناسیون نوترکیبsustained virological response - پاسخ ویروسی بالقوه
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
An effective hepatitis C virus (HCV) vaccine should elicit robust humoral and cell mediated immunity (CMI). A small animal challenge model is required to assess the efficacy of vaccines which elicit CMI. In this study, HCV proteins were expressed in hepatocytes of immunocompetent mice after hydrodynamic injection of a plasmid encoding the HCV NS3/4A protein. This vector, constructed as the “challenge”, was optimized for long term, specific gene expression in hepatocytes. To monitor HCV antigen expression in transfected hepatocytes, the plasmid also encoded secreted alkaline phosphatase (SEAP), which was detected in the mouse serum. The design of this novel challenge plasmid was based on studies using luciferase and SEAP as reporter molecules to examine the kinetics of the proteins expressed in hepatocytes and secreted into blood. We designed two constructs to control SEAP expression. In one construct, SEAP expression was controlled by the EMCV IRES, while in the other, a SEAP and luciferase polyprotein was cleaved by the FMDV2A proteinase. We found that SEAP expressed after FMDV2A self cleavage was more sensitive and showed a higher correlation with luciferase expressed in liver. The NS3/4A challenge model using the FMDV2A design provided a window period of 50 days to monitor changes in SEAP expression after hydrodynamic injection of DNA. In a challenge experiment, mice which received an adenovirus-based HCV vaccine showed accelerated clearance of SEAP and thus, of NS3/4A positive hepatocytes compared with a mock vaccinated group, that coincided with an increased number of CD8+ lymphocytes in the liver.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 32, Issue 27, 5 June 2014, Pages 3409-3416
Journal: Vaccine - Volume 32, Issue 27, 5 June 2014, Pages 3409-3416
نویسندگان
Wenbo Yu, Branka Grubor-Bauk, Tessa Gargett, Tamsin Garrod, Eric J. Gowans,