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肉毒杆菌神经毒素B型重组C片段(rBoNTB(HC))在恒河猴体内的免疫反应及保护作用

Recombinant C fragment of botulinum neurotoxin B serotype (rBoNTB (HC)) immune response and protection in the rhesus monkey.

作者信息

Boles James, West Michael, Montgomery Vicki, Tammariello Ralph, Pitt M Louise M, Gibbs Paul, Smith Leonard, LeClaire Ross D

机构信息

US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.

出版信息

Toxicon. 2006 Jun 15;47(8):877-84. doi: 10.1016/j.toxicon.2006.02.013. Epub 2006 Mar 24.

DOI:10.1016/j.toxicon.2006.02.013
PMID:16730042
Abstract

Botulinum neurotoxin B (BoNTB) is a distinct protein subtype of a family of neurotoxins with the potential for use in biological warfare or terrorist attacks. This study is one in a series evaluating the immunogenicity and protective effects of recombinant vaccines against the different subtypes of botulinum toxin. The recombinant subunit vaccines encoding the C fragment portion ( approximately 50 kDa) of the toxins are produced in the yeast, Pichia pastoris. In this study, groups of rhesus monkeys were vaccinated with three doses (1 and 5microg per dose) of rBoNTB(H(c)) vaccine. Total and neutralizing antibody titers were determined at various times during and postvaccination. Two groups of vaccinated monkeys plus non-vaccinated controls were actively challenged with B toxin by aerosol exposure. All monkeys receiving vaccine were protected from the toxin and no clinical signs of disease were observed, while controls displaying classic signs of botulism succumbed to the toxin challenge. Two additional groups of monkeys receiving the same vaccine regiment as the first two groups had significant levels of circulating neutralizing antibody titers up to 24 months postvaccination. This non-human primate study demonstrated the short- and long-term immunity afforded by the rBoNTB(H(c)) vaccine.

摘要

肉毒杆菌神经毒素B(BoNTB)是神经毒素家族中一种独特的蛋白质亚型,有被用于生物战或恐怖袭击的可能。本研究是评估重组疫苗针对不同亚型肉毒杆菌毒素的免疫原性和保护作用系列研究之一。编码毒素C片段部分(约50 kDa)的重组亚单位疫苗在毕赤酵母中生产。在本研究中,给恒河猴分组接种三剂(每剂1和5微克)rBoNTB(H(c))疫苗。在接种期间及接种后不同时间测定总抗体和中和抗体滴度。两组接种疫苗的猴子加未接种疫苗的对照通过气溶胶暴露接受B毒素的主动攻击。所有接种疫苗的猴子均受到毒素保护,未观察到疾病的临床症状,而表现出肉毒中毒典型症状的对照死于毒素攻击。另外两组接受与前两组相同疫苗方案的猴子在接种后长达24个月时循环中和抗体滴度显著升高。这项非人灵长类动物研究证明了rBoNTB(H(c))疫苗提供的短期和长期免疫力。

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