Recombinant L-HN Fusion Antigen Derived from the L and HN Domains of Botulinum Neurotoxin B Stimulates a Protective Antibody Response Against Active Neurotoxin.
Botulinum neurotoxin
Immunoprotective efficacy
Neutralizing antibody
Recombinant L-HN fusion antigen
Vaccine
Journal
Neurotoxicity research
ISSN: 1476-3524
Titre abrégé: Neurotox Res
Pays: United States
ID NLM: 100929017
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
31
10
2020
accepted:
27
01
2021
revised:
25
01
2021
pubmed:
23
2
2021
medline:
18
12
2021
entrez:
22
2
2021
Statut:
ppublish
Résumé
Botulinum neurotoxin (BoNT) is a neurotoxin produced by Clostridium botulinum in an anaerobic environment. BoNT is the most toxic protein among bacteria, animals, plants, and chemical substances reported to date. BoNTs are 150 kDa proteins composed of three major functional domains: catalytic (L domain, 50 kDa), translocation (HN domain, 50 kDa), and receptor-binding (Hc domain, 50 kDa) domains. Most studies have focused on the use of the Hc domain as an antigen because it is capable of generating robust protective immunity and contains some functional neutralizing epitopes. In the present study, we produced and characterized a recombinant L-HN fusion fragment of the parent BoNT/B (BL-HN) composed of L and HN domains with a deletion in the Hc domain (BHc). When the BL-HN protein was expressed in E. coli, it retained its stable structure and antigenicity. As a vaccine antigen, the recombinant BL-HN protein was found to induce sufficient protection against native BoNT/B in a mouse model. The BL-HN subunit vaccine could also induce a strong humoral immune response and generate sufficient neutralizing antibodies in immunized mice. Therefore, BL-HN may retain the native neurotoxin structure and critical epitopes responsible for inducing serum neutralizing antibodies. Studies of the dose-dependent immunoprotective effects further confirmed that the BL-HN antigen could provide potent protective immunity. This finding suggests that BL-HN can play an important role in immune protection against BoNT/B. Therefore, the BL-HN fusion fragment provides an excellent platform for the design of recombinant botulinum vaccines and neutralizing antibodies.
Identifiants
pubmed: 33616873
doi: 10.1007/s12640-021-00337-x
pii: 10.1007/s12640-021-00337-x
doi:
Substances chimiques
Antibodies, Bacterial
0
Antigens, Bacterial
0
Recombinant Proteins
0
antigen L
0
rimabotulinumtoxinB
0Y70779M1F
Botulinum Toxins, Type A
EC 3.4.24.69
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1044-1053Subventions
Organisme : National Major Research and Development Program of China
ID : 2017YFC1200902
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
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