Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E
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 recept...
Published in: | Infection and Immunity |
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Main Authors: | , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
American Society for Microbiology
2005
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Subjects: | |
Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230911 http://www.ncbi.nlm.nih.gov/pubmed/16177380 https://doi.org/10.1128/IAI.73.10.6998-7005.2005 |
Summary: | 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 α-rHCR/A1 recognized epitopes within the C terminus of the HCR/A and HCR/E, while α-rHCR/E recognized epitopes within the N terminus or interface between the N and C termini of the HCR proteins. α-rHCR/EB sera possessed detectable neutralizing capacity for BoNT/A1, while α-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. |
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