کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484206 | 1114303 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Production and Characterization of Chemically Inactivated Genetically Engineered Clostridium difficile Toxoids
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Production and Characterization of Chemically Inactivated Genetically Engineered Clostridium difficile Toxoids Production and Characterization of Chemically Inactivated Genetically Engineered Clostridium difficile Toxoids](/preview/png/2484206.png)
چکیده انگلیسی
A recombinant Clostridium difficile expression system was used to produce genetically engineered toxoids A and B as immunogens for a prophylactic vaccine against C. difficile-associated disease. Although all known enzymatic activities responsible for cytotoxicity were genetically abrogated, the toxoids exhibited residual cytotoxic activity as measured in an in vitro cell-based cytotoxicity assay. The residual cytotoxicity was eliminated by treating the toxoids with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide. Mass spectrometry and amino acid analysis of the EDC-inactivated toxoids identified crosslinks, glycine adducts, and β-alanine adducts. Surface plasmon resonance analysis demonstrated that modifications resulting from the chemical treatment did not appreciably affect recognition of epitopes by both toxin A- and B-specific neutralizing monoclonal antibodies. Compared to formaldehyde-inactivated toxoids, the EDC/N-hydroxysuccinimide-inactivated toxoids exhibited superior stability in solution with respect to reversion of cytotoxic activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 7, July 2016, Pages 2032-2041
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 7, July 2016, Pages 2032-2041
نویسندگان
Eugene Vidunas, Antony Mathews, Michele Weaver, Ping Cai, Eun Hee Koh, Sujata Patel-Brown, Hailey Yuan, Zi-rong Zheng, Marjolaine Carriere, J. Erik Johnson, Jason Lotvin, Justin Moran,