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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-02-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2017.1405201 |
| _version_ | 1827809953976418304 |
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| author | Chi Ho Yu Dong Hyun Song Jun Young Choi Hae Eun Joe Woo Hyeon Jeong Gyeung Haeng Hur Young Kee Shin Seong Tae Jeong |
| author_facet | Chi Ho Yu Dong Hyun Song Jun Young Choi Hae Eun Joe Woo Hyeon Jeong Gyeung Haeng Hur Young Kee Shin Seong Tae Jeong |
| author_sort | Chi Ho Yu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T22:47:01Z |
| format | Article |
| id | doaj.art-908d4f6fb0014185a2e75f0dfc605833 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:47:01Z |
| publishDate | 2018-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-908d4f6fb0014185a2e75f0dfc6058332023-09-22T08:17:53ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2018-02-0114232933610.1080/21645515.2017.14052011405201A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxicationChi Ho Yu0Dong Hyun Song1Jun Young Choi2Hae Eun Joe3Woo Hyeon Jeong4Gyeung Haeng Hur5Young Kee Shin6Seong Tae Jeong7Agency for Defense DevelopmentAgency for Defense DevelopmentAbion R&D InstituteAgency for Defense DevelopmentAgency for Defense DevelopmentAgency for Defense DevelopmentCollege of Pharmacy, Seoul National UniversityAgency for Defense DevelopmentBotulinum 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.http://dx.doi.org/10.1080/21645515.2017.1405201botulinumguinea pigmousemutationrecombinant vaccine |
| spellingShingle | Chi Ho Yu Dong Hyun Song Jun Young Choi Hae Eun Joe Woo Hyeon Jeong Gyeung Haeng Hur Young Kee Shin Seong Tae Jeong A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxication Human Vaccines & Immunotherapeutics botulinum guinea pig mouse mutation recombinant vaccine |
| title | A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxication |
| title_full | A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxication |
| title_fullStr | A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxication |
| title_full_unstemmed | A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxication |
| title_short | A mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type A intoxication |
| title_sort | mutated recombinant subunit vaccine protects mice and guinea pigs against botulinum type a intoxication |
| topic | botulinum guinea pig mouse mutation recombinant vaccine |
| url | http://dx.doi.org/10.1080/21645515.2017.1405201 |
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