Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses
Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses
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DOI：
10.1128/jvi.01514-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Chen, Hualan
中科院分区：
文献类型：
--
作者：
Ge, Jinying;Deng, Guohua;Chen, Hualan
H5 N1型高致病性禽流感病毒（HPAIV）在我国持续蔓延，对动物和人类健康构成严重威胁。目前的流感疫苗策略具有限制，这阻止了它们在野外广泛接种动物中的有效使用。然而，纽卡斯尔病病毒（NDV）的疫苗株已成功地用于容易地对大量动物进行疫苗接种。本研究利用反向遗传学技术构建了表达H5亚型禽流感病毒血凝素（HA）的NDV。将来自HPAIV野鸟分离株A/Bar-headed goose/Qinghai/3/2005（115 N1）的野生型和突变型HA开放阅读框（ORF）插入到LaSota NDV疫苗株的P和M基因之间的基因间隔区中。稳定表达野生型和突变型HA基因的重组病毒经1日龄雏鸡脑内接种后均无毒副作用。单剂量的重组病毒在鸡中诱导NDV和AIV 115特异性抗体，并完全保护鸡免受致死剂量的强毒NDV和同源和异源115 N1 HPAIV的攻击。此外，用重组NDV疫苗免疫BALB/c小鼠产生H5 AIV特异性抗体，并完全保护免受同源和异源致死病毒攻击。本研究结果表明，重组NDV是一种既能预防NDV又能预防AIV感染的双价弱毒活疫苗。重组NDV疫苗也可能用于高危人群，以控制致命性禽流感的大流行传播。
H5N1 highly pathogenic avian influenza virus (HPAIV) has continued to spread and poses a significant threat to both animal and human health. Current influenza vaccine strategies have limitations that prevent their effective use for widespread inoculation of animals in the field. Vaccine strains of Newcastle disease virus (NDV), however, have been used successfully to easily vaccinate large numbers of animals. In this study, we used reverse genetics to construct a NDV that expressed an H5 subtype avian influenza virus (AIV) hemagglutinin (HA). Both a wild-type and a mutated HA open reading frame (ORF) from the HPAIV wild bird isolate, A/Bar-headed goose/Qinghai/3/2005 (115N1), were inserted into the intergenic region between the P and M genes of the LaSota NDV vaccine strain. The recombinant viruses stably expressing the wild-type and mutant HA genes were found to be innocuous after intracerebral inoculation of I-day-old chickens. A single dose of the recombinant viruses in chickens induced both NDV- and AIV 115-specific antibodies and completely protected chickens from challenge with a lethal dose of both velogenic NDV and homologous and heterologous 115N1 HPAIV. In addition, BALB/c mice immunized with the recombinant NDV-based vaccine produced H5 AIV-specific antibodies and were completely protected from homologous and heterologous lethal virus challenge. Our results indicate that recombinant NDV is suitable as a bivalent live attenuated vaccine against both NDV and AIV infection in poultry. The recombinant NDV vaccine may also have potential use in high-risk human individuals to control the pandemic spread of lethal avian influenza.