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