A recombinant vesicular stomatitis virus replicon vaccine protects chickens from highly pathogenic avian influenza virus (H7N1)

A recombinant vesicular stomatitis virus replicon vaccine protects chickens from highly pathogenic avian influenza virus (H7N1)
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DOI:
10.1016/j.vaccine.2008.12.019
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发表时间:
2009-02-18
期刊:
影响因子:
5.5
通讯作者:
Zimmer, Gert
Zimmer, Gert
中科院分区:
医学3区
文献类型:
--
作者:
Kalhoro, Nazeer H.;Veits, Jutta;Zimmer, Gert

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H5和H7亚型的高致病性禽流感病毒(HPAIV)在家禽中引起致命疾病(禽鼠疫),但也有人畜共患的可能。目前市售的疫苗往往不能提供足够的保护,也不能轻易区分接种疫苗的禽类和受感染的禽类。因此,许多国家不允许对家禽接种H5和H7 HPAIV疫苗,或者只有在获得特别许可后才能接种。以非传染性水疱性口炎病毒(VSV)为基础,制备了一种以HPAIV a /FPV/Rostock/34 (H7N1) HA抗原代替VSV G基因的重组标记疫苗。这种病毒,VSV* δ G(HA),在一个提供VSV G的辅助细胞系上繁殖。由于非互补细胞感染后没有产生子代病毒,因此该载体被列为生物安全一级生物(“安全”)。鸡通过肌肉注射途径免疫。用相同复制子加强接种后,可诱导高滴度的血清抗体,可中和H7N1和H7N7亚型禽流感病毒,但不能中和H5N2。接种疫苗的鸡对异源HPAIV a /chicken/Italy/445/99 (H7N1)具有致死剂量的保护作用。攻毒病毒的分泌在短期内显著减少。最后,通过简单的酶联免疫吸附试验可以区分接种鸡和感染鸡。我们认为VSV复制子有潜力被开发成高质量的疫苗,以保护家禽免受不同亚型的禽流感病毒。2009爱思唯尔有限公司版权所有。
Highly pathogenic avian influenza Viruses (HPAIV) of subtypes H5 and H7 cause fatal disease in poultry (fowl plague) but also have zoonotic potential. Currently commercially available vaccines often do not Provide sufficient protection and do not allow easy discrimination between vaccinated and infected birds. Therefore, vaccination of domestic Poultry against H5 and H7 HPAIV is not allowed in many countries, or is only possible after special permission has been provided. We generated a recombinant marker vaccine based on non-transmissible, vesicular stomatitis virus (VSV) expressing the HA antigen of HPAIV A/FPV/Rostock/34 (H7N1) in place of the VSV G gene. This virus, VSV*Delta G(HA), was propagated on a helper cell line providing VSV G in trans. Since no progeny virus was produced after infection of non-complementing cells, the vector was classified as biosafety level I organism ("safe"). Chickens were immunized via the intramuscular route. Following booster vaccination with the same replicons high titers of serum antibodies were induced, which neutralized avian influenza viruses of subtypes H7N1 and H7N7 but not H5N2. Vaccinated chickens were protected against a lethal dose of heterologous HPAIV A/chicken/Italy/445/99 (H7N1). Secretion of challenge virus was short-term and significantly reduced. Finally, it was possible to discriminate vaccinated chickens from infected ones by a simple ELISA assay. We propose that VSV replicons have the potential to be developed to high-quality vaccines for protection Of Poultry against different subtypes of avian influenza Viruses. (C) 2009 Elsevier Ltd. All rights reserved.