Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B
Botulinum neurotoxins (BoNTs) are potential biological weapons because of their high toxicity and mortality. Vaccination is an effective strategy to prevent botulism. The carboxyl-terminus of the heavy chain (Hc domain) is nontoxic and sufficient to generate protective immune responses against natur...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-03-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2018.1547613 |
| _version_ | 1797677401210093568 |
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| author | Dan-Yang Shi Bo-Yang Chen Yun-Yun Mao Guo Zhou Jian-Sheng Lu Yun-Zhou Yu Xiao-Wei Zhou Zhi-Wei Sun |
| author_facet | Dan-Yang Shi Bo-Yang Chen Yun-Yun Mao Guo Zhou Jian-Sheng Lu Yun-Zhou Yu Xiao-Wei Zhou Zhi-Wei Sun |
| author_sort | Dan-Yang Shi |
| collection | DOAJ |
| description | Botulinum neurotoxins (BoNTs) are potential biological weapons because of their high toxicity and mortality. Vaccination is an effective strategy to prevent botulism. The carboxyl-terminus of the heavy chain (Hc domain) is nontoxic and sufficient to generate protective immune responses against natural BoNTs in animals. To produce a vaccine suitable for human use, a recombinant non His-tagged isoform of the Hc domain of botulinum neurotoxin serotype B (BHc) was expressed in Escherichia coli and purified by sequential chromatography. The immunogenicity of recombinant E.coli-expressed BHc and the yeast-expressed mBHc antigens was explored and compared in Balb/c mice. BHc provided comparable protective potency but elicited significantly higher antibody titer and neutralization potency against BoNT/B after twice immunization, indicating that the recombinant BHc protein expressed in E.coli have better immunogenicity than the yeast-expressed mBHc. Moreover, a frequency and dose-dependent effect was observed in mice immunized with BHc subunit vaccine and the anti-BHc ELISA antibody titers correlated well with neutralizing antibody titers and protection potency. In summary, the Alhydrogel-formulated BHc subunit vaccine afforded effective protection against BoNT/B challenge. Therefore, the non-His-tagged and homogeneous BHc expressed in E.coli represents a good potential candidate subunit vaccine for human use. |
| first_indexed | 2024-03-11T22:44:41Z |
| format | Article |
| id | doaj.art-4a06bc4d6b6e427cbe4429ce7c364220 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:44:41Z |
| publishDate | 2019-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-4a06bc4d6b6e427cbe4429ce7c3642202023-09-22T08:38:25ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2019-03-0115375576010.1080/21645515.2018.15476131547613Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype BDan-Yang Shi0Bo-Yang Chen1Yun-Yun Mao2Guo Zhou3Jian-Sheng Lu4Yun-Zhou Yu5Xiao-Wei Zhou6Zhi-Wei Sun7Beijing Institute of BiotechnologyBeijing Institute of BiotechnologyBeijing Institute of BiotechnologyBeijing Institute of BiotechnologyBeijing Institute of BiotechnologyBeijing Institute of BiotechnologyBeijing Institute of BiotechnologyBeijing Institute of BiotechnologyBotulinum neurotoxins (BoNTs) are potential biological weapons because of their high toxicity and mortality. Vaccination is an effective strategy to prevent botulism. The carboxyl-terminus of the heavy chain (Hc domain) is nontoxic and sufficient to generate protective immune responses against natural BoNTs in animals. To produce a vaccine suitable for human use, a recombinant non His-tagged isoform of the Hc domain of botulinum neurotoxin serotype B (BHc) was expressed in Escherichia coli and purified by sequential chromatography. The immunogenicity of recombinant E.coli-expressed BHc and the yeast-expressed mBHc antigens was explored and compared in Balb/c mice. BHc provided comparable protective potency but elicited significantly higher antibody titer and neutralization potency against BoNT/B after twice immunization, indicating that the recombinant BHc protein expressed in E.coli have better immunogenicity than the yeast-expressed mBHc. Moreover, a frequency and dose-dependent effect was observed in mice immunized with BHc subunit vaccine and the anti-BHc ELISA antibody titers correlated well with neutralizing antibody titers and protection potency. In summary, the Alhydrogel-formulated BHc subunit vaccine afforded effective protection against BoNT/B challenge. Therefore, the non-His-tagged and homogeneous BHc expressed in E.coli represents a good potential candidate subunit vaccine for human use.http://dx.doi.org/10.1080/21645515.2018.1547613botulinum neurotoxinhc domaincandidate subunit vaccine |
| spellingShingle | Dan-Yang Shi Bo-Yang Chen Yun-Yun Mao Guo Zhou Jian-Sheng Lu Yun-Zhou Yu Xiao-Wei Zhou Zhi-Wei Sun Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B Human Vaccines & Immunotherapeutics botulinum neurotoxin hc domain candidate subunit vaccine |
| title | Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B |
| title_full | Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B |
| title_fullStr | Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B |
| title_full_unstemmed | Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B |
| title_short | Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B |
| title_sort | development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype b |
| topic | botulinum neurotoxin hc domain candidate subunit vaccine |
| url | http://dx.doi.org/10.1080/21645515.2018.1547613 |
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