Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization
Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization
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DOI：
10.1128/jvi.80.4.1959-1964.2006
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发表时间：
2006-02-01
影响因子：
5.4
通讯作者：
Gambotto, A
中科院分区：
文献类型：
--
作者：
Gao, WT;Soloff, AC;Gambotto, A
最近在东南亚家禽中出现的高致病性禽流感病毒（HPAI）毒株及其随后向人类的传播引起了人们对致命疾病潜在大流行传播的担忧。在本文中，我们描述了一种基于腺病毒的甲型流感病毒疫苗的开发和测试针对血凝素（RA）蛋白的A/越南/1203/2004（H5 N1）（VN/1203/04）株在致命的人类疫情在越南从2003年至2005年。我们从重组复制缺陷型腺病毒载体中表达了RA的不同部分，在获得病毒序列的36天内实现了疫苗生产。用初免-加强疫苗免疫BALB/c小鼠，并在70天后暴露于致死剂量的VN/1203/04 H5 N1病毒的鼻内。疫苗接种诱导HA特异性抗体和细胞免疫可能提供异型免疫。用全长RA疫苗接种的小鼠被完全保护免于VN/1203/04的攻击。考虑到禽类在全球高致病性禽流感传播中的关键作用，我们接下来评估了基于腺病毒的疫苗接种在家禽中的效果。单次皮下免疫完全保护鸡免受21天后用VN/1203/04的鼻内攻击，其证明在2天内对所有对照接种的鸡是致命的。这些数据表明，快速生产重组腺病毒为基础的疫苗，并随后管理的鸟类和高风险的个人在面对爆发可能有助于控制致命的禽流感的大流行传播。
The recent emergence of highly pathogenic avian influenza virus (HPAI) strains in poultry and their subsequent transmission to humans in Southeast Asia have raised concerns about the potential pandemic spread of lethal disease. In this paper we describe the development and testing of an adenovirus-based influenza A virus vaccine directed against the hemagglutinin (RA) protein of the A/Vietnam/1203/2004 (H5N1) (VN/1203/04) strain isolated during the lethal human outbreak in Vietnam from 2003 to 2005. We expressed different portions of RA from a recombinant replication-incompetent adenoviral vector, achieving vaccine production within 36 days of acquiring the virus sequence. BALB/c mice were immunized with a prime-boost vaccine and exposed to a lethal intranasal dose of VN/1203/04 H5N1 virus 70 days later. Vaccination induced both HA-specific antibodies and cellular immunity likely to provide heterotypic immunity. Mice vaccinated with full-length RA were fully protected from challenge with VN/1203/04. We next evaluated the efficacy of adenovirus-based vaccination in domestic chickens, given the critical role of fowl species in the spread of HPAI worldwide. A single subcutaneous immunization completely protected chickens from an intranasal challenge 21 days later with VN/1203/04, which proved lethal to all control-vaccinated chickens within 2 days. These data indicate that the rapid production and subsequent administration of recombinant adenovirus-based vaccines to both birds and high-risk individuals in the face of an outbreak may serve to control the pandemic spread of lethal avian influenza.