UNASSIGNED: Botulinum neurotoxins (BoNTs) are responsible for @entity1 @entity6938 , a life-threatening disease characterized by flaccid @entity4589 that occurs naturally by food poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. BoNTs have been classified as category A agents by the Centers for Disease Control and Prevention. To date, 7 subtypes of BoNT/B were identified showing that subtypes B1 (16 strains) and B2 (32 strains) constitute the vast majority of BoNT/B strains. Neutralizing antibodies are required for the development of anti- @entity6938 drugs to deal with the potential risk. In this study, macaques ( @entity5434 ) were immunized with recombinant light chain (LC) or @entity11728 ( @entity11728 ) of BoNT/B2, followed by the construction of 2 hyper-immune phage display libraries. The best single-chain variable fragments (scFvs) isolated from each library were selected according to their affinities and cross reactivity with BoNT/B1 toxin subtype. These scFvs against LC and @entity11728 were further analyzed by assessing the inhibition of in vitro endopeptidase activity of BoNT/B1 and B2 and neutralization of BoNT/B1 and B2 toxin-induced @entity912 in the @entity19 ex vivo phrenic nerve assay. The antibodies B2-7 (against @entity11728 ) and BLC3 (against LC) were produced as @entity10390 -Fc, and, when tested individually, neutralized BoNT/B1 and BoNT/B2 in a @entity19 ex vivo phrenic nerve assay. Whereas only @entity10390 -Fc BLC3 alone protected @entity19 against BoNT/B2-induced @entity912 in vivo, when B2-7 and BLC3 were combined they exhibited potent synergistic protection. The present study provided an opportunity to assess the extent of antibody-mediated neutralization of BoNT/B1 and BoNT/B2 subtypes in ex vivo and in vitro assays, and to confirm the benefit of the synergistic effect of antibodies targeting the 2 distinct functional domains of the toxin in vivo. Notably, the framework regions of the most promising antibodies (B2-7 and BLC3) are close to the @entity1 germline sequences, which suggest that they may be well tolerated in potential clinical development.

Development of XXXX -like @entity10390 -Fc antibodies neutralizing Botulinum toxin serotype B.

@entity1 :: ('9606', 'Species') :: ['human'] @entity4589 :: ('MESH:D012133', 'Disease') :: ['muscle paralysis'] @entity912 :: ('MESH:D010243', 'Disease') :: ['paralysis'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5434 :: ('9541', 'Species') :: ['Macaca fascicularis'] @entity11728 :: ('MESH:D006362', 'Disease') :: ['HC', 'heavy chain'] @entity10390 :: ('652070', 'Gene') :: ['scFv'] @entity6938 :: ('MESH:D001906', 'Disease') :: ['botulism']
@entity1 :: (9606,Species) :: ['human']
