A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxication

Botulinum neurotoxins (BoNTs) are the most potent toxins to mammals. A toxoid vaccine was previously used for prevention of botulinum intoxication; however, this vaccine is no longer available. Currently, no approved botulinum vaccines are available from the Food and Drug Administration (FDA). Recen...

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Bibliographic Details
Published in:Human vaccines & immunotherapeutics 2018-02, Vol.14 (2), p.329-336
Main Authors: Yu, Chi Ho, Song, Dong Hyun, Choi, Jun Young, Joe, Hae Eun, Jeong, Woo Hyeon, Hur, Gyeung Haeng, Shin, Young Kee, Jeong, Seong Tae
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Bacterial Vaccines - immunology
Binding Sites
Botulinum
Botulinum Toxins, Type A - genetics
Botulinum Toxins, Type A - immunology
Botulism - prevention & control
Cell Line
Gangliosides - chemistry
Gangliosides - metabolism
guinea pig
Guinea Pigs
Immunoglobulin G - blood
Mice
Models, Molecular
mouse
mutation
Neurons - drug effects
Neurons - metabolism
Point Mutation
Protein Conformation
Protein Subunits
Recombinant Proteins - immunology
recombinant vaccine
Research Paper
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Summary:Botulinum neurotoxins (BoNTs) are the most potent toxins to mammals. A toxoid vaccine was previously used for prevention of botulinum intoxication; however, this vaccine is no longer available. Currently, no approved botulinum vaccines are available from the Food and Drug Administration (FDA). Recently, a recombinant host cell receptor-binding subunit created for use as a potential vaccine completed phase 2 clinical trials. The current study designed a vaccine candidate against BoNT type A (BoNT/A) using a structural design. Our vaccine candidate was the BoNT/A heavy chain C-terminal region (HCR) that contained the point mutation BA15 (R1269A) within the ganglioside-binding site. A Biacore affinity test showed that the affinity of BA15 for ganglioside GT1b was 100 times lower than that of the HCR. A SNAP25 cleavage assay revealed that immunized sera blocked SNAP25 cleavage of the BoNT/A toxin via BA15. In an in vivo experiment, mice and guinea pigs immunized with BA15 produced neutralizing antibodies that protected against 3,000 LD 50 of BoNT/A. In conclusion, the results of both in vitro and in vivo assays showed that our BA15 vaccine candidate was similar to the recombinant host cell receptor-binding subunit vaccine. The inability of BA15to bind ganglioside shows that BA15 is a potential safe vaccine candidate.
ISSN:2164-5515
2164-554X
DOI:10.1080/21645515.2017.1405201