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首页> 外文期刊>Clinical and vaccine immunology: CVI >A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates
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A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates

机译:一种人类Replication-Defective 5Adenovirus-Based三价疫苗所带来的在老鼠和完成预防瘟疫非人灵长类动物

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Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis. We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models.
机译:目前,在美国不存在鼠疫疫苗州供人类使用。或F1)和两个3型分泌系统(T3SS)组件,low-calcium-response V抗原(LcrV)和针蛋白质YscF,代表鼠疫杆菌的保护性抗原。replication-defective人类5型腺病毒(Ad5)向量和构建的重组单价和三价疫苗(rAd5-LcrV和rAd5-YFV)表示的codon-optimized lcrV或融合基因指定YFV (caf1 ycsF组成的,lcrV)。rAd5-YFV疫苗通过肌注(坜)或鼻内(i.n)路线保护优于单价rAd5-LcrV黑死疫苗和肺炎与Y鼠疫动物挑战时。耶CO92。不减少保护性反应,当老鼠保护总是更高管理一个i.n.剂量的三价疫苗(启动)单个i.m.紧随其后。升压剂纯化YFV抗原。免疫的猕猴猴三价疫苗rAd5-YFV启动—提高预防策略提供100%严格的剂量的CO92气溶胶的挑战既存的adenoviral免疫动物。接种疫苗和猕猴没有挑战疾病的迹象,入侵的病原体迅速清除,没有组织病理学病变。adenovirus-vectored三价的功效在鼠标和肺鼠疫疫苗非人灵长类动物模型(额定马力)。

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