Protection of mice against lethal infection with highly pathogenic H7N7 influenza A virus by using a recombinant low-pathogenicity vaccine strain
Protection of mice against lethal infection with highly pathogenic H7N7 influenza A virus by using a recombinant low-pathogenicity vaccine strain
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DOI：
10.1128/jvi.79.19.12401-12407.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Fouchier, RAM
中科院分区：
文献类型：
--
作者：
de Wit, E;Munster, VJ;Fouchier, RAM
2003年，荷兰爆发了高致病性禽流感。在88名患有结膜炎或轻度呼吸道症状的人和一名死于肺炎和急性呼吸窘迫综合征的人中也发现了导致疫情的禽流感H7 N7病毒。在这里，我们描述了一个小鼠模型的致命感染A/Nethertands/219/03分离的致命的情况下。由于H7 N7病毒的人畜共患病和致病潜力，通过反向遗传学产生了携带在高通量疫苗株A/PR/8/34的背景下产生的禽血凝素和神经氨酸酶蛋白的候选疫苗，并在小鼠模型中进行了测试。重组疫苗株的血凝素基因来源于在暴发之前从野生野鸭获得的低致病性病毒。比较了经典的无佐剂亚单位疫苗和免疫刺激复合物佐剂疫苗的效力。接受无佐剂疫苗的小鼠显示抗体滴度低，缺乏临床保护，肺中病毒滴度高，脾、肝、肾和脑中存在病毒。相比之下，接受两剂免疫刺激复合物佐剂疫苗的小鼠显示出高抗体滴度，临床保护，肺部病毒滴度降低1,000倍，其他器官中很少检测到病毒。这是第一份在哺乳动物模型中测试H7候选疫苗的报告。所提供的数据表明，如果使用有效的佐剂，可以在大流行威胁之前制备的基于低致病性禽流感A病毒的候选疫苗可能是有效的。
In 2003, an outbreak of highly pathogenic avian influenza occurred in the Netherlands. The avian H7N7 virus causing the outbreak was also detected in 88 humans suffering from conjunctivitis or mild respiratory symptoms and one person who died of pneumonia and acute respiratory distress syndrome. Here we describe a mouse model for lethal infection with A/Nethertands/219/03 isolated from the fatal case. Because of the zoonotic and pathogenic potential of the H7N7 virus, a candidate vaccine carrying the avian hemagglutinin and neuraminidase proteins produced in the context of the high-throughput vaccine strain A/PR/8/34 was generated by reverse genetics and tested in the mouse model. The hemagglutinin gene of the recombinant vaccine strain was derived from a low-pathogenicity virus obtained prior to the outbreak from a wild mallard. The efficacy of a classical nonadjuvanted subunit vaccine and an immune stimulatory complex-adjuvanted vaccine was compared. Mice receiving the nonadjuvanted vaccine revealed low antibody titers, lack of clinical protection, high virus titers in the lungs, and presence of virus in the spleen, liver, kidneys, and brain. In contrast, mice receiving two doses of the immune stimulatory complex-adjuvanted vaccine revealed high antibody titers, clinical protection, similar to 1,000-fold reduction of virus titers in the lungs, and rare detection of the virus in other organs. This is the first report of an H7 vaccine candidate tested in a mammalian model. The data presented suggest that vaccine candidates based on low-pathogenicity avian influenza A viruses, which can be prepared ahead of pandemic threats, can be efficacious if an effective adjuvant is used.