Development of a Molecular Engineered Vaccine for C. Botulinum Neurotoxins

Abstract

Recent work involving recombinant tetanus neurotoxin fragments demonstrate the “C fragment” (H_c domain) is a good vaccine candidate. This report describes initial efforts to determine if botulinum neurotoxin H_c fragments will also elicit aprotective immune response. Using clones encoding part of the heavy chain, gene segment constructs were designed to produce a native H_c polypeptide or an H_c polypeptide fused to E. coli maltose binding protein. Problems were encountered with both systems. Specifically, the construct for the native protein appeared to be unstable, while the fusion product appeared to be packaged in inclusion bodies that formed insoluble aggregates. Preliminary trials with animals indicated that vaccination with the fusion product conferred protection against native toxin challenge.