Immunization with reverse-genetics-produced H5N1 influenza vaccine protects ferrets against homologous and heterologous challenge
Immunization with reverse-genetics-produced H5N1 influenza vaccine protects ferrets against homologous and heterologous challenge
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DOI：
10.1086/505225
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发表时间：
2006-07-15
影响因子：
6.4
通讯作者：
Webster, Robert G.
中科院分区：
文献类型：
--
作者：
Govorkova, Elena A.;Webby, Richard J.;Webster, Robert G.
背景资料。H5N1禽流感病毒向人类传播的多个案例表明，迫切需要一种有效的、交叉保护的疫苗。用A/HK/213/03株血凝素(HA)和神经氨酸酶基因反向遗传制备的全病毒灭活疫苗免疫雪貂。雪貂接种含氢氧化铝佐剂的单剂疫苗(7或15 mgHA)或不含佐剂的2剂疫苗(各7 mg)，然后分别用A/HK/213/03、A/HK/156/97或A/越南/1203/04病毒的50%鸡蛋感染量攻击。一剂或两剂疫苗可诱导对疫苗株的保护性抗体反应。所有免疫方案均完全保护雪貂免受同源野生型A/HK/213/03病毒的攻击：未观察到临床症状，病毒复制显著减少(P<；0.05)，并局限于上呼吸道，防止了病毒向脑内传播。重要的是，所有接种疫苗的雪貂都能抵抗高致病毒株A/越南/1203/04的致命攻击。2剂方案诱导了更高水平的抗体，这些抗体对抗原性不同的H5N1病毒具有交叉反应。H5N1疫苗可能会激发一种比体外检测预测的更具交叉保护性的免疫反应，因此有可能被储存为“初始”大流行疫苗。
Background. Multiple cases of transmission of avian H5N1 influenza viruses to humans illustrate the urgent need for an efficacious, cross-protective vaccine.Methods. Ferrets were immunized with inactivated whole-virus vaccine produced by reverse genetics with the hemagglutinin (HA) and neuraminidase genes of A/HK/213/03 virus. Ferrets received a single dose of vaccine (7 or 15 mu g of HA) with aluminum hydroxide adjuvant or 2 doses (7 mg of HA each) without adjuvant and were challenged with 10(6) 50% egg infectious doses of A/HK/213/03, A/HK/156/97, or A/Vietnam/1203/04 virus.Results. One or 2 doses of vaccine induced a protective antibody response to the vaccine strain. All immunization regimens completely protected ferrets from challenge with homologous wild-type A/HK/213/03 virus: no clinical signs of infection were observed, virus replication was significantly reduced (P < .05) and was restricted to the upper respiratory tract, and spread of virus to the brain was prevented. Importantly, all vaccinated ferrets were protected against lethal challenge with the highly pathogenic strain A/Vietnam/1203/04. The 2-dose schedule induced higher levels of antibodies that were cross-reactive to antigenically distinct H5N1 viruses.Conclusions. H5N1 vaccines may stimulate an immune response that is more cross-protective than what might be predicted by in vitro assays and, thus, hold potential for being stockpiled as "initial" pandemic vaccines.