A three monoclonal antibody combination potently neutralizes multiple botulinum neurotoxin serotype F subtypesReportar como inadecuado




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Human botulism is primarily caused by botulinum neurotoxin BoNT serotypes A, B and E, with around 1% caused by serotype F BoNT-F. BoNT-F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies mAbs that can bind, detect and neutralize all BoNT-F subtypes. We used repertoire cloning of immune mouse antibody variable V regions and yeast display to generate a panel of 33 lead single chain Fv scFv mAbs that bound one or more BoNT-F subtypes with a median equilibrium dissociation constant KD of 4.06 × 10−9 M. By diversifying the V-regions of the lead mAbs and selecting for cross reactivity we generated five mAbs that bound each of the seven subtypes. Three scFv binding non-overlapping epitopes were converted to IgG that had KD for the different BoNT-F subtypes ranging from 2.2×10−8 M to 1.47×10−12 pM. An equimolar combination of the mAbs was able to potently neutralize BoNT-F1, F2, F4 and F7 in the mouse neutralization assay. The mAbs have potential utility as diagnostics capable of recognizing the known BoNT-F subtypes and could be developed as antitoxins to prevent and treat type F botulism.



Autor: Yongfeng Fan, Consuelo Garcia-Rodriguez, Jianlong Lou, Weihua Wen, Fraser Conrad, Wenwu Zhai, Theresa J. Smith, Leonard A. Smith,

Fuente: http://plos.srce.hr/



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