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用新型重组新城疫病毒载体疫苗对鸡进行母源免疫保护以抵抗禽流感病毒(AIV)。

Protection of Chickens with Maternal Immunity Against Avian Influenza Virus (AIV) by Vaccination with a Novel Recombinant Newcastle Disease Virus Vector.

机构信息

Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany.

出版信息

Avian Dis. 2020 Dec 1;64(4):427-436. doi: 10.1637/aviandiseases-D-20-00014.

Abstract

Newcastle disease virus (NDV) vectors expressing avian influenza virus (AIV) hemagglutinin of subtype H5 protect specific pathogen-free chickens from Newcastle disease and avian influenza. However, maternal AIV antibodies (AIV-MDA+) are known to interfere with active immunization by influencing vaccine virus replication and gene expression, resulting in inefficient protection. To overcome this disadvantage, we inserted a transgene encoding a truncated soluble hemagglutinin (HA) in addition to the gene encoding membrane-bound HA from highly pathogenic avian influenza virus (HPAIV) H5N1 into lentogenic NDV Clone 30 genome (rNDVsolH5_H5) to overexpress H5 antigen. Vaccination of 3-wk-old AIV-MDA+ chickens with rNDVsolH5_H5 and subsequent challenge infection with HPAIV H5N1 3 wk later resulted in 100% protection. Vaccination of younger chickens with higher AIV-MDA levels 1 and 2 wk after hatch resulted in protection rates of 40% and 85%, respectively. However, all vaccinated chickens showed strongly reduced shedding of challenge virus compared with age-matched, nonvaccinated control chickens. All control chickens succumbed to the HPAIV infection with a grading in disease progression between the three groups, indicating the influence of AIV-MDAs even at a low level. Furthermore, the shedding and serologic data gathered after immunization indicate sufficient replication of the vaccine virus, which leads to the assumption that lower protection rates in younger AIV-MDA+ chickens are caused by an H5 antigen-specific block and not by the interference of the AIV-MDA and the vaccine virus itself. In summary, solid protective efficacy and reduced virus transmission were achieved in 3-wk-old AIV-MDA+ chickens, which is relevant especially in regions endemically infected with HPAIV H5N1.

摘要

新城疫病毒(NDV)载体表达的禽流感病毒(AIV)血凝素亚型 H5 可保护无特定病原体鸡免受新城疫和禽流感的侵害。然而,已知母源 AIV 抗体(AIV-MDA+)会通过影响疫苗病毒复制和基因表达来干扰主动免疫,从而导致保护效果不佳。为了克服这一缺点,我们在除了编码高致病性禽流感病毒(HPAIV)H5N1 膜结合 HA 基因之外,还插入了一个编码截断可溶性 HA(HA)的转基因到弱毒 NDV Clone 30 基因组(rNDVsolH5_H5)中,以过表达 H5 抗原。3 周龄 AIV-MDA+鸡接种 rNDVsolH5_H5 并在 3 周后用 HPAIV H5N1 进行攻毒感染,结果 100%得到保护。在孵化后 1 周和 2 周时,用更高水平的 AIV-MDA 对较年轻的鸡进行接种,保护率分别为 40%和 85%。然而,与年龄匹配的未接种对照鸡相比,所有接种鸡的攻毒病毒脱落均明显减少。所有对照鸡均死于 HPAIV 感染,三组之间的疾病进展分级表明,即使在低水平时,AIV-MDAs 也会产生影响。此外,免疫接种后的病毒脱落和血清学数据表明疫苗病毒的充分复制,这表明在年轻的 AIV-MDA+鸡中较低的保护率是由 H5 抗原特异性阻断引起的,而不是由 AIV-MDA 和疫苗病毒本身的干扰引起的。总之,在 3 周龄的 AIV-MDA+鸡中实现了牢固的保护效力和降低的病毒传播,这在高致病性禽流感病毒 H5N1 地方性流行的地区尤为相关。

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