Enhancing toxin-based vaccines against botulism.

ABSTRACT: 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 (HC_N) and a receptor binding domain (HC_C). Currently, there are no approved vaccines against botulism. This study tests a recombinant, full-length BoNT/A1 versus LCHC_N/A1 and HC_C/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 m

SUBMITTER: Przedpelski A 

PROVIDER: S-EPMC5820173 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature