کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8486057 | 1551762 | 2018 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enhancing toxin-based vaccines against botulism
ترجمه فارسی عنوان
افزایش واکسن های مبتنی بر توکسین علیه بوتولیسم
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کلمات کلیدی
LD50HCNIC50SNARETeNTBoNTHCC - HCCbotulism - بوتولیسمELISA - تست الیزاTetanus toxin - سموم تتراBotulinum neurotoxin - نوروتوکسین بوتولینومBotulinum neurotoxins - نوروتوکسین بوتولینومhalf maximal inhibitory concentration - نیمه حداکثر غلظت مهاریVaccine - واکسنsoluble NSF attachment protein receptor - گیرنده پروتئینی پروتئین دلبستگی NSF محلول است
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
چکیده انگلیسی
Botulinum neurotoxins (BoNT) are the most toxic proteins for humans. BoNTs are single chain proteins with an N-terminal light chain (LC) and a C-terminal heavy chain (HC). HC comprises a translocation domain (HCN) and a receptor binding domain (HCC). Currently, there are no approved vaccines against botulism. This study tests a recombinant, full-length BoNT/A1 versus LCHCN/A1 and HCC/A1 as vaccine candidates against botulism. Recombinant, full-length BoNT/A1 was detoxified by engineering 3-amino acid mutations (E224A/R363A/Y366F) (M-BoNT/A1) into the LC to eliminate catalytic activity, which reduced toxicity in a mouse model of botulism by >106-fold relative to native BoNT/A1. As a second step to improve vaccine safety, an additional mutation (W1266A) was engineered in the ganglioside binding pocket, resulting in reduced receptor binding, to produce M-BoNT/A1W. M-BoNT/A1W vaccination protected against challenge by 106 LD50 Units of native BoNT/A1, while M-BoNT/A1 or M-BoNT/A1W vaccination equally protected against challenge by native BoNT/A2, a BoNT subtype. Mice vaccinated with M-BoNT/A1W surviving BoNT challenge had dominant antibody responses to the LCHCN domain, but varied antibody responses to HCC. Sera from mice vaccinated with M-BoNT/A1W also neutralized BoNT/A1 action on cultured neuronal cells. The cell- and mouse-based assays measured different BoNT-neutralizing antibodies, where M-BoNT/A1W elicited a strong neutralizing response in both assays. Overall, M-BoNT/A1W, with defects in multiple toxin functions, elicits a potent immune response to BoNT/A challenge as a vaccine strategy against botulism and other toxin-mediated diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 36, Issue 6, 1 February 2018, Pages 827-832
Journal: Vaccine - Volume 36, Issue 6, 1 February 2018, Pages 827-832
نویسندگان
Amanda Przedpelski, William H. Tepp, Madison Zuverink, Eric A. Johnson, Sabine Pellet, Joseph T. Barbieri,