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重组 H5 禽痘病毒和新城疫病毒载体的初免-加强免疫可在 SPF 番鸭中提供针对高致病性 H5N1 流感病毒的持久保护。

Prime-boost vaccination with recombinant H5-fowlpox and Newcastle disease virus vectors affords lasting protection in SPF Muscovy ducks against highly pathogenic H5N1 influenza virus.

机构信息

Anses (French Agency for Food, Environmental and Occupational Health Safety), Ploufragan/Plouzané Laboratory, Avian and Rabbit Virology Immunology and Parasitology Unit (VIPAC), B.P. 53, 22440 Ploufragan, France.

出版信息

Vaccine. 2013 Aug 28;31(38):4121-8. doi: 10.1016/j.vaccine.2013.06.074. Epub 2013 Jul 8.

DOI:10.1016/j.vaccine.2013.06.074
PMID:23845804
Abstract

Vaccination protocols were evaluated in one-day old Muscovy ducklings, using an experimental Newcastle disease recombinant vaccine (vNDV-H5) encoding an optimized synthetic haemagglutinin gene from a clade 2.2.1 H5N1 highly pathogenic (HP) avian influenza virus (AIV), either as a single administration or as a boost following a prime inoculation with a fowlpox vectored vaccine (vFP89) encoding a different H5 HP haemagglutinin from an Irish H5N8 strain. These vaccination schemes did not induce detectable levels of serum antibodies in HI test using a clade 2.2.1 H5N1 antigen, and only induced H5 ELISA positive response in less than 10% of vaccinated ducks. However, following challenge against a clade 2.2.1 HPAIV, both protocols afforded full clinical protection at six weeks of age, and full protection against mortality at nine weeks. Only the prime-boost vaccination (vFP89+vNDV-H5) was still fully protecting Muscovy ducks against disease and mortality at 12 weeks of age. Reduction of oropharyngeal shedding levels was also constantly observed from the onset of the follow-up at 2.5 or three days post-infection in vaccinated ducks compared to unvaccinated controls, and was significantly more important for vFP89+vNDV-H5 vaccination than for vNDV-H5 alone. Although the latter vaccine is shown immunogenic in one-day old Muscovy ducks, the present work is original in demonstrating the high efficacy of the successive administration of two different vector vaccines encoding two different H5 in inducing lasting protection (at least similar to the one induced by an inactivated reassortant vaccine, Re-5). In addition, such a prime-boost schedule allows implementation of a DIVA strategy (to differentiate vaccinated from infected ducks) contrary to Re-5, involves easy practice on the field (with injection at the hatchery and mass vaccination later on), and should avoid eventual interference with NDV maternally derived antibodies. Last, the HA insert could be updated according to the epidemiological situation.

摘要

对 1 日龄麝香鸭进行了疫苗接种方案评估,使用一种实验性的新城疫重组疫苗(vNDV-H5),该疫苗编码来自 2.2.1 分支的高致病性(HP)禽流感病毒(AIV)的一种经过优化的合成血凝素基因,作为单次给药,或在使用编码来自爱尔兰 H5N8 株的不同 HP 血凝素的禽痘病毒载体疫苗(vFP89)进行基础免疫接种后进行加强免疫。这些接种方案在使用 2.2.1 分支 H5N1 抗原的 HI 试验中未诱导可检测水平的血清抗体,并且仅在不到 10%的接种鸭中诱导 H5 ELISA 阳性反应。然而,在针对 2.2.1 分支的 HPAIV 进行攻毒后,两种方案均在 6 周龄时提供完全的临床保护,在 9 周龄时提供完全的死亡率保护。只有基础免疫加强免疫(vFP89+vNDV-H5)在 12 周龄时仍能完全保护麝香鸭免受疾病和死亡率的影响。与未接种对照组相比,从接种鸭在感染后 2.5 或 3 天开始的随访开始,口咽分泌物脱落水平也不断降低,并且对于 vFP89+vNDV-H5 接种比单独接种 vNDV-H5 更为重要。尽管该疫苗已在 1 日龄麝香鸭中显示出免疫原性,但本研究的创新性在于证明了连续接种两种不同载体疫苗(编码两种不同的 H5)可诱导持久保护的高效性(至少与灭活重组疫苗 Re-5 诱导的保护相似)。此外,这种基础免疫加强免疫方案允许实施区分疫苗接种鸭和感染鸭的 DIVA 策略(与 Re-5 相反),涉及在现场进行简单的实践(在孵化场进行注射,然后进行大规模接种),并且应避免与 NDV 母源抗体的任何干扰。最后,HA 插入物可以根据流行病学情况进行更新。

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