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重组禽副粘病毒2型、6型和10型作为携带新城疫病毒抗体鸡的高致病性禽流感疫苗载体

Recombinant Avian Paramyxovirus Serotypes 2, 6, and 10 as Vaccine Vectors for Highly Pathogenic Avian Influenza in Chickens with Antibodies Against Newcastle Disease Virus.

作者信息

Tsunekuni Ryota, Hikono Hirokazu, Tanikawa Taichiro, Kurata Riho, Nakaya Takaaki, Saito Takehiko

机构信息

A Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0854, Japan.

B National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0854, Japan.

出版信息

Avian Dis. 2017 Sep;61(3):296-306. doi: 10.1637/11512-100616-RegR1.

DOI:10.1637/11512-100616-RegR1
PMID:28957006
Abstract

Recombinant Newcastle disease virus (rNDV) expressing the hemagglutinin of highly pathogenic avian influenza virus (HPAIV HA) induces protective immunity against HPAIV in chickens. However, the efficacy of rNDV vectors is hampered when chickens are pre-immune to NDV, and most commercial chickens are routinely vaccinated against NDV. We recently showed that avian paramyxovirus serotypes 2, 6, and 10 (APMV-2, APMV-6, and APMV-10), which belong to the same genus as NDV, have low cross-reactivity with anti-NDV antisera. Here, we used reverse genetics to generate recombinant APMV-2, APMV-6, and APMV-10 (rAPMV-2/HA, rAPMV-6/HA, and rAPMV-10/HA) that expressed an HA protein derived of subtype H5N1 HPAIV, A/chicken/Yamaguchi/7/2004. Chickens pre-immunized against NDV (age, 7 wk) were vaccinated with rAPMV/HAs; 14 days after vaccination, chickens were challenged with a lethal dose of HPAIV. Immunization of chickens pre-immunized against NDV with rAPMV-2/HA, rAPMV-6/HA, or rAPMV-10/HA protected 50%, 50%, and 25%, respectively, in groups of chickens given an rAPMV/HA with 106 median embryo infectious dose (EID) or 50%, 50%, and 90%, respectively, in those with 10 EID; in contrast, rNDV/HA protected none of the chicken vaccinated with 10 EID and induced only partial protection even with 10 EID Therefore, the presence of anti-NDV antibodies did not hamper the efficacy of rAPMV-2/HA, rAPMV-6/HA, or rAPMV-10/HA. These results suggest that rAPMV-2, rAPMV-6, and rAPMV-10 are potential vaccine vectors, especially for commercial chickens, which are routinely vaccinated against NDV.

摘要

表达高致病性禽流感病毒(HPAIV)血凝素的重组新城疫病毒(rNDV)可诱导鸡对HPAIV产生保护性免疫。然而,当鸡预先免疫过新城疫病毒时,rNDV载体的效力会受到影响,而大多数商业鸡群通常都接种过新城疫病毒疫苗。我们最近发现,与新城疫病毒属于同一属的禽副粘病毒血清型2、6和10(APMV - 2、APMV - 6和APMV - 10)与抗新城疫病毒抗血清的交叉反应性较低。在此,我们利用反向遗传学技术构建了表达源自H5N1亚型HPAIV(A/鸡/山口/7/2004)的血凝素蛋白的重组APMV - 2、APMV - 6和APMV - 10(rAPMV - 2/HA、rAPMV - 6/HA和rAPMV - 10/HA)。预先免疫过新城疫病毒的鸡(7周龄)接种rAPMV/HAs;接种后14天,用致死剂量的HPAIV对鸡进行攻毒。用rAPMV - 2/HA、rAPMV - 6/HA或rAPMV - 10/HA对预先免疫过新城疫病毒的鸡进行免疫,在给予106个鸡胚半数感染剂量(EID)的rAPMV/HA组中,分别有50%、50%和25%的鸡得到保护;在给予10个EID的组中,分别有50%、50%和90%的鸡得到保护;相比之下,rNDV/HA在接种10个EID时未能保护任何一只鸡,即使接种106个EID也仅诱导了部分保护。因此,抗新城疫病毒抗体的存在并未妨碍rAPMV - 2/HA、rAPMV - 6/HA或rAPMV - 10/HA的效力。这些结果表明,rAPMV - 2、rAPMV - 6和rAPMV - 10是潜在的疫苗载体,特别是对于常规接种新城疫病毒疫苗的商业鸡群。

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