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PMID: 16177380 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Characterization of the antibody response to the receptor binding domain of botulinum neurotoxin serotypes A and E.

Infection and immunity ·Vol. 73 ·No. 10 ·2005-10-00 ·Pages 6998-7005

Baldwin MR, Tepp WH, Pier CL, Bradshaw M, Ho M, Wilson BA, Fritz RB, Johnson EA, Barbieri JT

Abstract

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/E(B)) 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/E(B) 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/E(A)), while rHCR/E(B) neutralized BoNT/E(A), 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/E(B) to BoNT/E(A) 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.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Bacterial/blood,immunology,pharmacology Bacterial Vaccines/chemistry,immunology Botulinum Toxins/antagonists & inhibitors,chemistry,immunology Botulinum Toxins, Type A/antagonists & inhibitors,chemistry,genetics,immunology Clostridium botulinum/immunology Escherichia coli/genetics Mice Molecular Sequence Data Peptide Fragments/genetics,immunology Protein Conformation Rabbits
Chemicals
Antibodies, Bacterial Bacterial Vaccines Peptide Fragments botulinum neurotoxin A (844-1250) botulinum neurotoxin A (870-1295) Botulinum Toxins Botulinum Toxins, Type A botulinum toxin type E
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Baldwin Michael R
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, 53226, USA.
Tepp William H
Pier Christina L
Bradshaw Marite
Ho Mengfei
Wilson Brenda A
Fritz Robert B
Johnson Eric A
Barbieri Joseph T
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.73.10.6998-7005.2005
Published
2005-10-00
Pages
6998-7005
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC1230911
Subset
IM
Grants
NIAID NIH HHS · U54 AI057153 · United States
NIAID NIH HHS · U54 AI065359 · United States
External Links
PubMed source DOI: 10.1128/IAI.73.10.6998-7005.2005 PMC Full Text View journal details
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