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

• Main Authors: Chi Ho Yu (Author), Dong Hyun Song (Author), Jun Young Choi (Author), Hae Eun Joe (Author), Woo Hyeon Jeong (Author), Gyeung Haeng Hur (Author), Young Kee Shin (Author), Seong Tae Jeong (Author)
• Format: Book
• Published: Taylor & Francis Group, 2018-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

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 LD50 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.

Item Description

2164-5515
2164-554X
10.1080/21645515.2017.1405201