Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E
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-cha...
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crasmicro:10.1128/iai.73.10.6998-7005.2005 2023-11-05T03:40:51+01:00 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 http://dx.doi.org/10.1128/iai.73.10.6998-7005.2005 https://journals.asm.org/doi/pdf/10.1128/IAI.73.10.6998-7005.2005 en eng American Society for Microbiology https://journals.asm.org/non-commercial-tdm-license Infection and Immunity volume 73, issue 10, page 6998-7005 ISSN 0019-9567 1098-5522 Infectious Diseases Immunology Microbiology Parasitology journal-article 2005 crasmicro https://doi.org/10.1128/iai.73.10.6998-7005.2005 2023-10-09T15:57:27Z 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 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/E B 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/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. Article in Journal/Newspaper Beluga Beluga* Alaska ASM Journals (American Society for Microbiology - via Crossref) Infection and Immunity 73 10 6998 7005 |
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Open Polar |
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ASM Journals (American Society for Microbiology - via Crossref) |
op_collection_id |
crasmicro |
language |
English |
topic |
Infectious Diseases Immunology Microbiology Parasitology |
spellingShingle |
Infectious Diseases Immunology Microbiology Parasitology 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 |
Infectious Diseases Immunology Microbiology Parasitology |
description |
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 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/E B 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/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. |
format |
Article in Journal/Newspaper |
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://dx.doi.org/10.1128/iai.73.10.6998-7005.2005 https://journals.asm.org/doi/pdf/10.1128/IAI.73.10.6998-7005.2005 |
genre |
Beluga Beluga* Alaska |
genre_facet |
Beluga Beluga* Alaska |
op_source |
Infection and Immunity volume 73, issue 10, page 6998-7005 ISSN 0019-9567 1098-5522 |
op_rights |
https://journals.asm.org/non-commercial-tdm-license |
op_doi |
https://doi.org/10.1128/iai.73.10.6998-7005.2005 |
container_title |
Infection and Immunity |
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73 |
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10 |
container_start_page |
6998 |
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7005 |
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1781697081262473216 |