Development and evaluation of candidate subunit vaccine against botulinum neurotoxin serotype B

作者：Danyang Shi, Boyang Chen, Yunyun Mao, Guo Zhou, Jiansheng Lu, Yun‐Zhou Yu, Xiaowei Zhou, Zhiwei Sun · 发表于：Human Vaccines & Immunotherapeutics · 年份：2018 · DOI：10.1080/21645515.2018.1547613 · 被引用次数：16 · 研究领域：Botulinum Toxin and Related Neurological Disorders、Hereditary Neurological Disorders、Neurological disorders and treatments

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.