Tetanus toxin and botulinum neurotoxin-derived fusion molecules are effective bivalent vaccines.
Bivalent vaccine
BoNT/A
Functional domain
Immune protection
Receptor binding domain
TeNT
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
25
07
2023
accepted:
13
09
2023
revised:
06
09
2023
medline:
13
11
2023
pubmed:
24
9
2023
entrez:
23
9
2023
Statut:
ppublish
Résumé
Tetanus toxin (TeNT) and botulinum neurotoxins (BoNTs) are neuroprotein toxins, with the latter being the most toxic known protein. They are structurally similar and contain three functional domains: an N-terminal catalytic domain (light chain), an internal heavy-chain translocation domain (HN domain), and a C-terminal heavy chain receptor binding domain (Hc domain or RBD). In this study, fusion functional domain molecules consisting of the TeNT RBD (THc) and the BoNT/A RBD (AHc) (i.e., THc-Linker-AHc and AHc-Linker-THc) were designed, prepared, and identified. The interaction of each Hc domain and the ganglioside receptor (GT1b) or the receptor synaptic vesicle glycoprotein 2 (SV2) was explored in vitro. Their immune response characteristics and protective efficacy were investigated in animal models. The recombinant THc-linker-AHc and AHc-linker-THc proteins with the binding activity had the correct size and structure, thus representing novel subunit vaccines. THc-linker-AHc and AHc-linker-THc induced high levels of specific neutralizing antibodies, and showed strong immune protective efficacy against both toxins. The high antibody titers against the two novel fusion domain molecules and against individual THc and AHc suggested that the THc and AHc domains, as antigens in the fusion functional domain molecules, do not interact with each other and retain their full key epitopes responsible for inducing neutralizing antibodies. Thus, the recombinant THc-linker-AHc and AHc-linker-THc molecules are strong and effective bivalent biotoxin vaccines, protecting against two biotoxins simultaneously. Our experimental design will be valuable to develop recombinant double-RBD fusion molecules as potent bivalent subunit vaccines against bio-toxins. KEY POINTS: • Double-RBD fusion molecules from two toxins had the correct structure and activity. • THc-linker-AHc and AHc-linker-THc efficiently protected against both biotoxins. • Such bivalent biotoxin vaccines based on the RBD are a valuable experimental design.
Identifiants
pubmed: 37741939
doi: 10.1007/s00253-023-12796-7
pii: 10.1007/s00253-023-12796-7
doi:
Substances chimiques
Tetanus Toxin
0
Botulinum Toxins, Type A
EC 3.4.24.69
Antibodies, Neutralizing
0
Vaccines, Subunit
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7197-7211Subventions
Organisme : the Laboratory of Advanced Biotechnology Project
ID : BDZZ202204
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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