This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baldwin, M. R.
Right arrow Articles by Barbieri, J. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baldwin, M. R.
Right arrow Articles by Barbieri, J. T.

 Previous Article  |  Next Article 

Infection and Immunity, October 2005, p. 6998-7005, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6998-7005.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E

Michael R. Baldwin,1 William H. Tepp,2 Christina L. Pier,2 Marite Bradshaw,2 Mengfei Ho,3 Brenda A. Wilson,3 Robert B. Fritz,1 Eric A. Johnson,2 and Joseph T. Barbieri1*

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee,1 Food Research Institute, University of Wisconsin at Madison, Madison, Wisconsin,2 Department of Microbiology, University of Illinois at Urbana—Champaign, Illinois3

Received 5 March 2005/ Returned for modification 13 April 2005/ Accepted 22 June 2005

Clostridium botulinum neurotoxins (BoNTs) are the most toxic proteins for humans. The current clostridial-derived vaccines against BoNT intoxication have limitations including production and accessibility. Conditions were established to express the soluble receptor binding domain (heavy-chain receptor [HCR]) of BoNT serotypes A and E in Escherichia coli. Sera isolated from mice and rabbits immunized with recombinant HCR/A1 (rHCR/A1) from the classical type A-Hall strain (ATCC 3502) (BoNT/A1) and rHCR/E from BoNT serotype E Beluga (BoNT/EB) neutralized the homologous serotype of BoNT but displayed differences in cross-recognition and cross-protection. Enzyme-linked immunosorbent assay and Western blotting showed that {alpha}-rHCR/A1 recognized epitopes within the C terminus of the HCR/A and HCR/E, while {alpha}-rHCR/E recognized epitopes within the N terminus or interface between the N and C termini of the HCR proteins. {alpha}-rHCR/EB sera possessed detectable neutralizing capacity for BoNT/A1, while {alpha}-rHCR/A1 did not neutralize BoNT/E. rHCR/A was an effective immunogen against BoNT/A1 and the Kyoto F infant strain (BoNT/A2), but not BoNT serotype E Alaska (BoNT/EA), while rHCR/EB neutralized BoNT/EA, and under hyperimmunization conditions protected against BoNT/A1 and BoNT/A2. The protection elicited by rHCR/A1 to BoNT/A1 and BoNT/A2 and by rHCR/EB to BoNT/EA indicate that immunization with receptor binding domains elicit protection within sub-serotypes of BoNT. The protection elicited by hyperimmunization with rHCR/E against BoNT/A suggests the presence of common neutralizing epitopes between the serotypes E and A. These results show that a receptor binding domain subunit vaccine protects against serotype variants of BoNTs.

* 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.

Editor: D. L. Burns

Infection and Immunity, October 2005, p. 6998-7005, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6998-7005.2005
Copyright © 2005, 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]  
  • Baldwin, M. R., Tepp, W. H., Przedpelski, A., Pier, C. L., Bradshaw, M., Johnson, E. A., Barbieri, J. T. (2008). Subunit Vaccine against the Seven Serotypes of Botulism. Infect. Immun. 76: 1314-1318 [Abstract] [Full Text]  
  • Pier, C. L., Tepp, W. H., Bradshaw, M., Johnson, E. A., Barbieri, J. T., Baldwin, M. R. (2008). Recombinant Holotoxoid Vaccine against Botulism. Infect. Immun. 76: 437-442 [Abstract] [Full Text]  
  • Maddaloni, M., Staats, H. F., Mierzejewska, D., Hoyt, T., Robinson, A., Callis, G., Kozaki, S., Kiyono, H., McGhee, J. R., Fujihashi, K., Pascual, D. W. (2006). Mucosal Vaccine Targeting Improves Onset of Mucosal and Systemic Immunity to Botulinum Neurotoxin A. J. Immunol. 177: 5524-5532 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»