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Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.在健康志愿者中进行的开放标签、剂量递增的I期研究，以评估一种抗艰难梭菌毒素A人单克隆抗体的安全性和药代动力学。
Vaccine. 2008 Jun 25;26(27-28):3404-9. doi: 10.1016/j.vaccine.2008.04.042. Epub 2008 May 7.
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Design, construction, and characterization of a dual-promoter multigenic DNA vaccine directed against an HIV-1 subtype C/B' recombinant.针对HIV-1 C/B'重组亚型的双启动子多基因DNA疫苗的设计、构建及特性分析
J Acquir Immune Defic Syndr. 2008 Apr 1;47(4):403-11. doi: 10.1097/QAI.0b013e3181651b9d.
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Use of attenuated bacteria as delivery vectors for DNA vaccines.使用减毒细菌作为DNA疫苗的递送载体。
Expert Rev Vaccines. 2007 Feb;6(1):97-110. doi: 10.1586/14760584.6.1.97.
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Vaccine delivery methods using viral vectors.使用病毒载体的疫苗递送方法。
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Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier.以乙肝核心抗原作为免疫载体开发丙型肝炎病毒疫苗。
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Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and V antigens protects against bubonic and pneumonic plague.用同时表达鼠疫耶尔森菌F1和V抗原的沙门氏菌进行口服疫苗接种可预防腺鼠疫和肺鼠疫。
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一种靶向艰难梭菌毒素A受体结合域的DNA疫苗。

A DNA vaccine targeting the receptor-binding domain of Clostridium difficile toxin A.

作者信息

Gardiner David F, Rosenberg Talia, Zaharatos Jerry, Franco David, Ho David D

机构信息

Division of International Medicine and Infectious Diseases, Weill Cornell Medical College, New York, NY, United States.

出版信息

Vaccine. 2009 Jun 2;27(27):3598-604. doi: 10.1016/j.vaccine.2009.03.058. Epub 2009 Apr 9.

DOI:10.1016/j.vaccine.2009.03.058
PMID:19464540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2709243/
Abstract

Clostridium difficile is a pathogen with increasing severity for which host antibody responses provide protection from disease. DNA vaccination has several advantages compared to traditional vaccine methods, however no study has examined this platform against C. difficile toxins. A synthetic gene was created encoding the receptor-binding domain (RBD) of C. difficile toxin A, optimized for expression in human cells. Gene expression was examined in vitro. Mice were inoculated and then challenged with parenteral toxin A. Vaccination provided high titer antibodies and protected mice from death. This represents the first report of DNA vaccine inducing neutralizing antibodies to C. difficile toxin A.

摘要

艰难梭菌是一种致病性日益严重的病原体，宿主抗体反应可提供疾病防护。与传统疫苗方法相比，DNA疫苗接种有几个优点，然而尚无研究针对艰难梭菌毒素检测该平台。构建了一个合成基因，编码艰难梭菌毒素A的受体结合结构域（RBD），并针对在人细胞中的表达进行了优化。在体外检测了基因表达。给小鼠接种疫苗，然后用肠外毒素A进行攻击。疫苗接种产生了高滴度抗体并保护小鼠免于死亡。这是DNA疫苗诱导针对艰难梭菌毒素A的中和抗体的首次报道。