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首页> 外文期刊>Vaccine >Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens
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Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens

机译：表达H5血凝素的改良新城疫病毒载体可增强鸡对高致病性H5N1禽流感病毒的保护

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Naturally-occurring attenuated strains of Newcastle disease virus (NDV) are being developed as vaccine vectors for use in poultry and humans. However, some NDV strains, such as Beaudette C (BC), may retain too much virulence in poultry for safe use, and more highly attenuated strains may be suboptimally immunogenic. We therefore modified the BC strain by changing the multibasic cleavage site sequence of the F protein to the dibasic sequence of avirulent strain LaSota. Additionally, the BC, F, and HN proteins were modified in several ways to enhance virus replication. These modified BC-derived vectors and the LaSota strain were engineered to express the hemagglutin (HA) protein of H5N1 highly pathogenic influenza virus (HPAIV). In general, the modified BC-based vectors expressing HA replicated better than LaSota/HA, and expressed higher levels of HA protein. Pathogenicity tests indicated that all the modified viruses were highly attenuated in chickens. Based on in vitro characterization, two of the modified BC vectors were chosen for evaluation in chickens as vaccine vectors against H5N1 HPAIV A/Vietnam/1203/04. Immunization of chickens with rNDV vector vaccines followed by challenge with HPAIV demonstrated high levels of protection against clinical disease and mortality. However, only those chickens immunized with modified BC/HA in which residues 271-330 from the F protein had been replaced with the corresponding sequence from the NDV AKO strain conferred complete protection against challenge virus shedding. Our findings suggest that this modified rNDV can be used safely as a vaccine vector with enhanced replication, expression, and protective efficacy in avian species, and potentially in humans
机译：新城疫病毒（NDV）的天然减毒株正在开发作为用于家禽和人类的疫苗载体。然而，一些NDV菌株，如Beaudette C（BC），可能在家禽中保留了过多的毒力，无法安全使用，而更高度减毒的菌株可能免疫原性欠佳。因此，我们通过将 F 蛋白的多碱基切割位点序列更改为无毒菌株 LaSota 的二碱基序列来修改 BC 菌株。此外，BC、F 和 HN 蛋白以多种方式进行修饰以增强病毒复制。这些修饰的 BC 衍生载体和 LaSota 菌株被设计用于表达 H5N1 高致病性流感病毒 （HPAIV） 的血凝素 （HA） 蛋白。一般来说，表达HA的基于BC的修饰载体比LaSota/HA复制得更好，并且表达更高水平的HA蛋白。致病性试验表明，所有改良病毒在鸡体内均高度减毒。基于体外表征，选择两种改良的BC载体作为针对H5N1 HPAIV A/越南/1203/04的疫苗载体在鸡中进行评估。用rNDV载体疫苗对鸡进行免疫接种，然后用HPAIV进行攻击，显示出对临床疾病和死亡率的高水平保护。然而，只有那些用改良的BC / HA免疫的鸡，其中F蛋白的残基271-330已被NDV AKO菌株的相应序列取代，才能完全防止攻击病毒脱落。我们的研究结果表明，这种改良的rNDV可以安全地用作疫苗载体，在禽类物种中具有增强的复制、表达和保护效力，并可能在人类中发挥作用

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