The recombinant Hc subunit of Clostridium botulinum neurotoxin serotype A is an effective botulism vaccine candidate.
Vaccination with recombinant His-tagged isoforms of the Clostridium botulinum Hc domain of neurotoxin serotype A (rAHc) have effectively protected against challenge with active botulinum neurotoxin serotype A. To establish a formulation suitable for human use, rAHc was expressed in Escherichia coli without a His-tag and purified by sequential chromatography on ion-exchange and hydrophobic-interaction resins. Purified rAHc was used to vaccinate mice and survival was evaluated following challenge with active toxin. rAHc-vaccinated mice were protected against an active toxin challenge in mouse models of disease and a dose-response relationship was observed between the dose of rAHc administered and protection. Vaccination with rAHc in the presence or absence of adjuvants was also tested following intramuscular or subcutaneous vaccination to determine the optimal route of vaccination in the context of active toxin challenge. The data presented in the report suggested that rAHc administered with or without adjuvants functioned effectively over time in protecting mice against challenge with neurotoxin suggesting that this form of rAHc may be developed into a human vaccine candidate designed for the prevention of botulism.
Beijing Institute of Biotechnology, 20 Dong Dajie Street, Fengtai District, Beijing 100071, China.
Yun-Zhou
YZ
Yu
Na
N
Li
Heng-Qi
HQ
Zhu
Rui-Lin
RL
Wang
Yun
Y
Du
Shuang
S
Wang
Wei-Yuan
WY
Yu
Zhi-Wei
ZW
Sun
D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019274:Botulinum Toxins, Type A / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001906:Botulism / Q000276:immunology / Q000517:prevention & control*; D003014:Clostridium botulinum / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism
D001428:Bacterial Vaccines; D010456:Peptides, Cyclic; D021122:Protein Subunits; D011994:Recombinant Proteins; C037654:HC toxin; D019274:Botulinum Toxins, Type A