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1. 发明申请

WO2009092038A1 INFLUENZ DNA VACCINATION AND METHODS OF USE THEREOF 审中-公开
标题翻译： INFLUENZ DNA疫苗及其使用方法
公开(公告)号：WO2009092038A1
公开(公告)日：2009-07-23
申请号：PCT/US2009031329
申请日：2009-01-16
申请人： US GOV HEALTH & HUMAN SERV , RAO SRINIVAS , NABEL GARY J , YANG ZIH-YONG , WEI CHIH-JEN , KONG WING-PUI
发明人： RAO SRINIVAS , NABEL GARY J , YANG ZIH-YONG , WEI CHIH-JEN , KONG WING-PUI
IPC分类号： A61K39/145
CPC分类号： A61K39/145 , A61K39/12 , A61K2039/53 , A61K2039/54 , A61K2039/58 , A61K2039/70 , C07K14/005 , C12N2760/16122 , C12N2760/16134
摘要： Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in birds would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their inability to protect against evolving avian influenza viruses. DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes protect against homologous and heterologous HPAI H5N1 strain challenge in animals. These vaccines elicit antibodies that neutralize multiple serotypes of HPAI H5N1 when given in combinations containing up to 10 HAs. The response is dose-dependent. The breadth of protection is determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA immunogens and/or vaccines conferred complete protection in mice against lethal H5N1 A/Vietnam/ 1203/2004 challenge 68 weeks after vaccination. In chickens, complete protection was conferred against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device.
摘要翻译：高致病性禽流感（HPAI）H5N1在禽类物种中的持续爆发增加了重配和适应人类的风险。控制其在鸟类中传播的能力将减少这种威胁，并有助于维持基于蛋的疫苗生产的能力。虽然疫苗具有控制禽流感病毒的潜力，但目前疫苗的主要问题是其无法防止禽流感病毒进化。编码来自不同HPAI H5N1血清型的血凝素（HA）蛋白质的DNA疫苗保护动物免受同源和异源HPAI H5N1毒株攻击。当以最多10HA的组合给予时，这些疫苗引发中和多种血清型的HPAI H5N1的抗体。反应是剂量依赖性的。保护的广度由疫苗中流感病毒HA的选择决定。疫苗接种后68周，单价和三价HA免疫原和/或疫苗在小鼠中完全保护免于致死的H5N1 A /越南/ 1203/2004攻击。在鸡中，用三价H5血清型DNA疫苗接种后，通过肌内注射或无针装置给予两次，剂量低至5μg的DNA，对抗HPAI H5N1的异源菌株进行完全保护。

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