کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484349 | 1114308 | 2016 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Novel Ricin Subunit Antigens With Enhanced Capacity to Elicit Toxin-Neutralizing Antibody Responses in Mice
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کلمات کلیدی
DSCRTBNSETSEtNAricin toxin A chainRtaImmunology - ایمونولوژیTev - به توPhysical stability - ثبات فیزیکیMelting Temperature - دمای ذوبlethal dose - دوز مرگبارRicin - ریسینComputational biology - زیستشناسی محاسباتیProtein structure - ساختار پروتئینMolecular Operating Environment - محیط عملیاتی مولکولیVaccines - واکسنMOE - وزارت صنایعTobacco etch virus - ویروس تنباکو اچDifferential scanning calorimetry - کالریمتری روبشی افتراقی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
RiVax is a candidate ricin toxin subunit vaccine antigen that has proven to be safe in human phase I clinical trials. In this study, we introduced double and triple cavity-filling point mutations into the RiVax antigen with the expectation that stability-enhancing modifications would have a beneficial effect on overall immunogenicity of the recombinant proteins. We demonstrate that 2 RiVax triple mutant derivatives, RB (V81L/C171L/V204I) and RC (V81I/C171L/V204I), when adsorbed to aluminum salts adjuvant and tested in a mouse prime-boost-boost regimen were 5- to 10-fold more effective than RiVax at eliciting toxin-neutralizing serum IgG antibody titers. Increased toxin neutralizing antibody values and seroconversion rates were evident at different antigen dosages and within 7 days after the first booster. Quantitative stability/flexibility relationships analysis revealed that the RB and RC mutations affect rigidification of regions spanning residues 98-103, which constitutes a known immunodominant neutralizing B-cell epitope. A more detailed understanding of the immunogenic nature of RB and RC may provide insight into the fundamental relationship between local protein stability and antibody reactivity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 5, May 2016, Pages 1603-1613
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 5, May 2016, Pages 1603-1613
نویسندگان
Newton Wahome, Erin Sully, Christopher Singer, Justin C. Thomas, Lei Hu, Sangeeta B. Joshi, David B. Volkin, Jianwen Fang, John Karanicolas, Donald J. Jacobs, Nicholas J. Mantis, C. Russell Middaugh,