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...
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American Society for Microbiology
2005
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ftpubmed:oai:pubmedcentral.nih.gov:1230911 2023-05-15T15:41:55+02:00 Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E Baldwin, Michael R. Tepp, William H. Pier, Christina L. Bradshaw, Marite Ho, Mengfei Wilson, Brenda A. Fritz, Robert B. Johnson, Eric A. Barbieri, Joseph T. 2005-10 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 en eng American Society for Microbiology http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230911 http://www.ncbi.nlm.nih.gov/pubmed/16177380 http://dx.doi.org/10.1128/IAI.73.10.6998-7005.2005 Copyright © 2005, American Society for Microbiology Microbial Immunity and Vaccines Text 2005 ftpubmed https://doi.org/10.1128/IAI.73.10.6998-7005.2005 2013-08-30T14:34:37Z 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. Text Beluga Beluga* Alaska PubMed Central (PMC) Infection and Immunity 73 10 6998 7005 |
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topic |
Microbial Immunity and Vaccines |
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Microbial Immunity and Vaccines Baldwin, Michael R. Tepp, William H. Pier, Christina L. Bradshaw, Marite Ho, Mengfei Wilson, Brenda A. Fritz, Robert B. Johnson, Eric A. Barbieri, Joseph T. Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E |
topic_facet |
Microbial Immunity and Vaccines |
description |
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. |
format |
Text |
author |
Baldwin, Michael R. Tepp, William H. Pier, Christina L. Bradshaw, Marite Ho, Mengfei Wilson, Brenda A. Fritz, Robert B. Johnson, Eric A. Barbieri, Joseph T. |
author_facet |
Baldwin, Michael R. Tepp, William H. Pier, Christina L. Bradshaw, Marite Ho, Mengfei Wilson, Brenda A. Fritz, Robert B. Johnson, Eric A. Barbieri, Joseph T. |
author_sort |
Baldwin, Michael R. |
title |
Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E |
title_short |
Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E |
title_full |
Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E |
title_fullStr |
Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E |
title_full_unstemmed |
Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E |
title_sort |
characterization of the antibody response to the receptor binding domain of botulinum neurotoxin serotypes a and e |
publisher |
American Society for Microbiology |
publishDate |
2005 |
url |
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 |
genre |
Beluga Beluga* Alaska |
genre_facet |
Beluga Beluga* Alaska |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230911 http://www.ncbi.nlm.nih.gov/pubmed/16177380 http://dx.doi.org/10.1128/IAI.73.10.6998-7005.2005 |
op_rights |
Copyright © 2005, American Society for Microbiology |
op_doi |
https://doi.org/10.1128/IAI.73.10.6998-7005.2005 |
container_title |
Infection and Immunity |
container_volume |
73 |
container_issue |
10 |
container_start_page |
6998 |
op_container_end_page |
7005 |
_version_ |
1766374789232984064 |