Development of a Molecular Engineered Vaccine for C. Botulinum Neurotoxins
Recent work involving recombinant tetanus neurotoxin fragments demonstrate the “C fragment” (Hc domain) is a good vaccine candidate. This report describes initial efforts to determine if botulinum neurotoxin Hc fragments will also elicit aprotective immune response. Using clones encoding part of the heavy chain, gene segment constructs were designed to produce a native Hc polypeptide or an Hc 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.
KeywordsBotulinum Toxin Fusion Product Maltose Binding Protein Botulinum Neurotoxin Tetanus Toxin
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- 2.DasGupta BR, Sugiyama H. Limited proteolysis of Clostridium botulinum types A and B neurotoxin. Am Soc Microbiol 1978: 25.Google Scholar
- 4.Kozaki S, Kamata Y, Takahashi M, Shimizu T, Sakaguchi G. Antibodies against botulism neurotoxin. In: Simpson LL, ed. Botulism Neurotoxin and Tetanus Neurotoxin, New York: Academic Press, 1989.Google Scholar
- 6.Makoff AJ, Ballantine SP, Smallwood AE, Fairweather NF. Expression of tetanus toxin fragment C in E. coli: its purification and potential as a vaccine. Biotechnology 1989; 7: 1043–1046.Google Scholar