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Infection and Immunity, March 2008, p. 1314-1318, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01025-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Subunit Vaccine against the Seven Serotypes of Botulism{triangledown}

Michael R. Baldwin,1 William H. Tepp,2 Amanda Przedpelski,1 Christina L. Pier,2 Marite Bradshaw,2 Eric A. Johnson,2 and Joseph T. Barbieri1*

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin,1 Food Research Institute, University of Wisconsin—Madison, Madison, Wisconsin2

Received 25 July 2007/ Returned for modification 4 September 2007/ Accepted 19 November 2007

Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans and are classified as category A toxins. There are seven serotypes of BoNTs defined by the lack of cross-serotype toxin neutralization. Thus, an effective vaccine must neutralize each BoNT serotype. BoNTs are organized as dichain A-B toxins, where the N-terminal domain (light chain) is a zinc metalloprotease targeting soluble NSF attachment receptor proteins that is linked to the C-terminal domain (heavy chain [HC]) by a disulfide bond. The HC comprises a translocation domain and a C-terminal receptor binding domain (HCR). HCRs of the seven serotypes of BoNTs (hepta-HCR) were engineered for expression in Escherichia coli, and each HCR was purified from E. coli lysates. Immunization of mice with the E. coli-derived hepta-serotype HCR vaccine elicited an antibody response to each of the seven BoNT HCRs and neutralized challenge by 10,000 50% lethal doses of each of the seven BoNT serotypes. A solid-phase assay showed that the anti-hepta-serotype HCR sera inhibited the binding of HCR serotypes A and B to the ganglioside GT1b, the first step in BoNT intoxication of neurons. This is the first E. coli-derived vaccine that effectively neutralizes each of the seven BoNT serotypes.

* Corresponding author. Mailing address: Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Phone: (414) 456-8412. Fax: (414) 456-6535. E-mail: jtb01{at}mcw.edu

{triangledown} Published ahead of print on 10 December 2007.

Editor: S. R. Blanke

Infection and Immunity, March 2008, p. 1314-1318, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01025-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yu, Y.-Z., Li, N., Wang, R.-L., Zhu, H.-Q., Wang, S., Yu, W.-Y., Sun, Z.-W. (2008). Evaluation of a Recombinant Hc of Clostridium botulinum Neurotoxin Serotype F as an Effective Subunit Vaccine. CVI 15: 1819-1823 [Abstract] [Full Text]  
  • Keller, J. E. (2008). Characterization of New Formalin-Detoxified Botulinum Neurotoxin Toxoids. CVI 15: 1374-1379 [Abstract] [Full Text]  


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