New genetic vaccine to protect aganist botulism

新型基因疫苗可保护无肉毒杆菌中毒

• 批准号: 6673546
• 负责人: MINGTAO ZENG
• 金额: $ 31.5万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6673546
• 关键词: Adenoviridae; Clostridium botulinum; active immunization; antiviral antibody; botulinum toxins; botulism; colony stimulating factor; enzyme linked immunosorbent assay; inhalation drug administration; laboratory mouse; mucosal immunity; neurotoxins; neutralizing antibody; polymerase chain reaction; tissue /cell culture; topical drug application; toxoids; vaccine development; vector vaccine; western blottings

DESCRIPTION (provided by applicant): Botulism is a severe neuroparalytic disease caused by one of seven botulinum neurotoxins (BoNTs), produced by the anaerobic, spore-forming bacterium Clostridium botulinum. These protein neurotoxins are the most potent toxins known to man. There are BoNT toxoid vaccines available currently as Investigational New Drugs. However, due to the numerous shortcomings associated with the toxoid vaccines (i.e., dangerous to produce, high cost of manufacturing, high reactogenicity), there is an urgent need to develop new generation vaccines for the prevention of botulism. The goals of this research are to develop a new botulism vaccine using the carboxyl-terminal 50 kDa C-fragments (Hc) of the heavy chains in BoNTs as antigens and to study the delivery of the vaccine utilizing a replication-defective adenoviral vector via the intranasal and transcutaneous routes. These non-invasive vaccine delivery methods will undoubtedly enhance the compliance of a vaccination program, which is especially critical in response to a potential bioterrorist attack using BoNTs. After construction of replication-defective adenoviral vectors encoding the immunogenic C-fragments of the heavy chains in BoNTs, vaccination protocols in mice comparing the intranasal and transcutaneous delivery modes with the subcutaneous injection of the currently available pentavalent botulinum toxoid vaccine (PBT) will be studied. The specific aims of this project are: Specific Aim #1: To construct replication-defective adenoviral vectors encoding the C-fragments of the heavy chains in BoNTs. Specific Aim #2: To study the mucosal and systemic immunity elicited by the vectored vaccine developed in aim #1 through intranasal and transcutaneous immunization in a mouse model.

描述（由申请人提供）：肉毒杆菌是由一种由厌氧，形成孢子的细菌肉毒杆菌蛋白酶产生的七种肉毒神经毒素（BONTS）引起的严重神经分析疾病。这些蛋白质神经毒素是人类已知的最有效的毒素。目前有BONT毒素疫苗作为研究新药。但是，由于与毒素疫苗相关的许多缺点（即生产危险，制造高成本，高反应生成性），因此迫切需要开发新一代疫苗以预防肉毒杆菌主义。这项研究的目标是使用抗原作为抗原的重链的羧基末端50 kDa c-fragments（HC）开发一种新的肉毒杆菌疫苗，并利用复制性腺病毒载体通过抗原的抗原进行了疫苗的传递。鼻内和经皮路线。这些非侵入性疫苗输送方法无疑将增强疫苗接种计划的依从性，这对于使用BONT的潜在生物恐怖攻击尤其至关重要。在构建了复制缺陷的腺病毒载体后，编码重链中重链的免疫原性的C碎片，在小鼠中进行疫苗接种方案，将乳腺内和经经态递送模式与当前可用的五型肉毒杆菌疫苗（PBT）进行比较。 该项目的具体目的是： 特定目的＃1：构建复制缺陷型腺病毒载体编码bonts中重链的C碎片。 具体目的＃2：研究在小鼠模型中通过鼻内和经态免疫在目标1中开发的矢量疫苗引起的粘膜和全身免疫力。