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腺病毒载体猪流感疫苗在小鼠中对不同抗原 H1N1 株的免疫效力。

Immune efficacy of an adenoviral vector-based swine influenza vaccine against antigenically distinct H1N1 strains in mice.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

出版信息

Antiviral Res. 2017 Nov;147:29-36. doi: 10.1016/j.antiviral.2017.09.009. Epub 2017 Sep 20.

Abstract

Avian-like H1N1 swine influenza viruses are prevalent in pigs and have occasionally crossed the species barrier and infected humans, which highlights the importance of preventing swine influenza. Human adenovirus serotype 5 (Ad5) has been tested in human influenza vaccine clinical trials and has exhibited a reliable safety profile. Here, we generated a replication-defective, recombinant adenovirus (designated as rAd5-avH1HA) expressing the hemagglutinin gene of an avian-like H1N1 virus (A/swine/Zhejiang/199/2013, ZJ/199/13). Using a BALB/c mouse model, we showed that a two-dose intramuscular administration of recombinant rAd5-avH1HA induced high levels of hemagglutination inhibition antibodies and prevented homologous and heterologous H1N1 virus-induced weight loss, as well as viral replication in the nasal turbinates and lungs of mice. Furthermore, a prime-boost immunization strategy trial with a recombinant plasmid (designated as pCAGGS-HA) followed by rAd5-avH1HA vaccine provided effective protection against homologous and heterologous H1N1 virus infection in mice. These results indicate that rAd5-avH1HA is an efficacious genetically engineered vaccine candidate against H1N1 swine influenza. Future studies should examine its immune efficacy in pigs.

摘要

禽源性 H1N1 猪流感病毒在猪群中流行,并偶尔跨越物种屏障感染人类,这突显了预防猪流感的重要性。人腺病毒 5 型(Ad5)已在人类流感疫苗临床试验中进行了测试,具有可靠的安全性。在这里,我们构建了一种复制缺陷型重组腺病毒(命名为 rAd5-avH1HA),该病毒表达了禽源性 H1N1 病毒(A/swine/Zhejiang/199/2013,ZJ/199/13)的血凝素基因。我们使用 BALB/c 小鼠模型表明,肌肉内给予两剂重组 rAd5-avH1HA 可诱导高水平的血凝抑制抗体,并可预防同源和异源 H1N1 病毒引起的体重减轻以及鼻甲骨和肺部的病毒复制。此外,重组质粒(命名为 pCAGGS-HA)进行初免-加强免疫策略试验后再接种 rAd5-avH1HA 疫苗,可有效保护小鼠免受同源和异源 H1N1 病毒感染。这些结果表明 rAd5-avH1HA 是一种针对 H1N1 猪流感的有效基因工程疫苗候选物。未来的研究应在猪中检测其免疫效果。

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