Generation of an attenuated H5N1 avian influenza virus vaccine with all eight genes from avian viruses.
Generation of an attenuated H5N1 avian influenza virus vaccine with all eight genes from avian viruses.
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DOI：
10.1016/j.vaccine.2007.08.011
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发表时间：
2007-10
期刊：
影响因子：
5.5
通讯作者：
Huoying Shi;Xiu-fan Liu;Xiaorong Zhang;Su-juan Chen;Lei Sun;Jian-hong Lu
中科院分区：
文献类型：
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作者：
Huoying Shi;Xiu-fan Liu;Xiaorong Zhang;Su-juan Chen;Lei Sun;Jian-hong Lu
面对禽类疾病暴发和H5N1亚型高致病性禽流感病毒（hpaiv）对人类造成的潜在大流行威胁，改善生物安全和使用灭活疫苗是控制该疾病的两个主要选择。H5N1亚型甲型流感病毒候选疫苗已在若干实验室通过质粒为基础的反向遗传学，利用禽流感流行毒株的血凝素（HA）和神经氨酸酶（NA）基因，以人毒株A/Puerto Rico/8/34 （PR8）疫苗供体毒株的内部基因为背景，制备出来。这些含有禽流感和人类病毒基因的重组病毒可能会引起生物安全问题，如果C4/F禽流感病毒是减毒活疫苗或冷适应株疫苗，也可能会引起生物安全问题。为了产生更好和更安全的候选疫苗病毒，我们利用禽毒株的8个基因，通过质粒反向遗传构建了减毒重组H5N1甲型流感病毒，命名为C4/F AIV。该病毒的HA和NA基因来源于A/Chicken/华东/04 （H5N1）流行毒株（C4/H5N1），其内部基因来源于A/Chicken/F/98（H9N2）低致病性毒株。重组病毒通过突变和删除HA基因中的多碱基氨基酸基序（从PQRERRRKKR↓G到PQIETR↓G）而减弱。供体病毒C4/F的静脉致病性指数为0，供体病毒C4/H5N1的静脉致病性指数为3.0。感染胚卵尿囊液中C4/H5N1病毒HA滴度高达1:2048。由重组病毒C4/ faiv制备的灭活疫苗在接种鸡体内引起高HI滴度，在H5N1亚型高致病性禽流感病毒攻毒时具有100%的保护作用。
In the face of disease outbreaks in poultry and the potential pandemic threat to humans caused by the highly pathogenic avian influenza viruses (HPAIVs) of H5N1 subtype, improvement in biosecurity and the use of inactivated vaccines are two main options for the control of this disease. Vaccine candidates of influenza A viruses of H5N1 subtype have been generated in several laboratories by plasmid-based reverse genetics with hemagglutinin (HA) and neuraminidase (NA) genes from the epidemic strains of avian viruses in a background of internal genes from the vaccine donor strain of human strains, A/Puerto Rico/8/34 (PR8). These reassortant viruses containing genes from both avian and human viruses might impose biosafety concerns, also may be do if C4/F AIV would be a live attenuated vaccine or cold-adaptive strain vaccine. In order to generate better and safer vaccine candidate viruses, we genetically constructed attenuated reassortant H5N1 influenza A virus, designated as C4/F AIV, by plasmid-based reverse genetics with all eight genes from the avian strains. The C4/F AIV virus contained HA and NA genes from an epidemic strain A/Chicken/Huadong/04 (H5N1) (C4/H5N1) in a background of internal genes derived from a low pathogenic strain of A/Chicken/F/98(H9N2). The reassortant virus was attenuated by removal of the multibasic amino acid motif in the HA gene by mutation and deletion (from PQRERRRKKR↓G to PQIETR↓G). The intravenous pathogenicity index (IVPI) of C4/F AIV virus was 0, whereas that of the donor virus C4/H5N1 was 3.0. The virus HA titer of C4/H5N1 in the allantoic fluid from infected embryonated eggs was as high as 1:2048. The inactivated vaccine prepared from the reassortant virus C4/F AIV-induced high HI titer in vaccinated chickens and gave 100% protection when challenged with highly pathogenic avian influenza virus of H5N1 subtype.