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首页> 外文期刊>Vaccine >Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice
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Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice

机译:委内瑞拉马脑炎病毒复制子介导的多剂疫苗可引发对马尔堡病毒的免疫反应,并能抵抗小鼠的炭疽和肉毒杆菌神经毒素

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摘要

The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.
机译:多剂疫苗的开发具有在较短的时间内以最小的接种量引发针对多种疾病的保护的优势。我们在这里报告了使用针对委内瑞拉马脑炎(VEE)病毒复制子载体的针对细菌性疾病,炭疽的疫苗配方的结果。病毒性疾病,马尔堡热;并抵抗毒素介导的疾病,肉毒中毒。单个VEE复制子颗粒(VRP)从炭疽芽孢杆菌表达成熟的83 kDa保护性抗原(MAT-PA),从马尔堡病毒(MBGV)表达的糖蛋白(GP)或从肉毒杆菌神经毒素(BoNT H( C))。接种表达VRP的BoNT H(C)血清型C(BoNT / CH(C))和MAT-PA混合物的CBA / J小鼠免受炭疽芽孢杆菌(Sterne株)攻击80%保护,然后100%免受连续的BoNT / C挑战。接种了单独VRP或表达A型BoNT H(C),Boot / A H(C),MAT-PA和MBGV-GP的VRP疫苗混合物的瑞士小鼠产生了对相应复制子表达蛋白特异的抗体反应。与仅接受一种VRP疫苗的小鼠相比,不同VRP疫苗的组合并未减少针对接种两种或三种VRP疫苗制剂的瑞士小鼠测得的抗体反应。单独接种表达VRP的BoNT / A H(C)或与表达VRP的MAT-PA和MBGV GP组合的瑞士小鼠受到BoNT / A攻击的完全保护。这些研究证明了将单个VRP疫苗组合成多剂制剂以引发针对各种类型疾病的保护性免疫应答的效用。

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