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表达致病性街狂犬病毒完整和截短糖蛋白及核蛋白的重组腺病毒单剂与联合使用在小鼠中的保护效力比较

Comparison of the protective efficacy between single and combination of recombinant adenoviruses expressing complete and truncated glycoprotein, and nucleoprotein of the pathogenic street rabies virus in mice.

作者信息

Kim Ha-Hyun, Yang Dong-Kun, Nah Jin-Ju, Song Jae-Young, Cho In-Soo

机构信息

Viral Disease Division, Animal and Plant Quarantine Agency, Gimcheon, 39660, MAFRA, Republic of Korea.

出版信息

Virol J. 2017 Jun 24;14(1):122. doi: 10.1186/s12985-017-0789-2.

Abstract

BACKGROUND

Rabies is an important viral zoonosis that causes acute encephalitis and death in mammals. To date, several recombinant vaccines have been developed based on G protein, which is considered to be the main antigen, and these vaccines are used for rabies control in many countries. Most recombinant viruses expressing RABV G protein retain the G gene from attenuated RABV. Not enough is currently known about the protective effect against RABV of a combination of recombinant adenoviruses expressing the G and N proteins of pathogenic street RABV.

METHODS

We constructed a recombinant adenovirus (Ad-0910Gsped) expressing the signal peptide and ectodomain (sped) of G protein of the Korean street strain, and evaluated the immunological protection conferred by a single and combination of three kinds of recombinant adenoviruses (Ad-0910Gsped and Ad-0910G with or without Ad-0910 N) in mice.

RESULTS

A combination of Ad-0910G and Ad-0910 N conferred improved immunity against intracranial challenge compared to single administration of Ad-0910G. The Ad-0910G virus, expressing the complete G protein, was more immunogenic than Ad-0910Gsped, which expressed a truncated G protein with the transmembrane and cytoplasmic domains removed. Additionally, oral vaccination using a combination of viruses led to complete protection.

CONCLUSIONS

Our results suggest that this combination of viruses is a viable new intramuscular and oral vaccine candidate.

摘要

背景

狂犬病是一种重要的病毒性人畜共患病,可导致哺乳动物患急性脑炎并死亡。迄今为止,已经基于被认为是主要抗原的G蛋白开发了几种重组疫苗,这些疫苗在许多国家用于狂犬病防控。大多数表达狂犬病病毒(RABV)G蛋白的重组病毒保留了来自减毒RABV的G基因。目前,关于表达致病性街毒株RABV的G和N蛋白的重组腺病毒组合对RABV的保护作用了解不足。

方法

我们构建了一种表达韩国街毒株G蛋白信号肽和胞外域(sped)的重组腺病毒(Ad-0910Gsped),并评估了三种重组腺病毒(Ad-0910Gsped以及有或没有Ad-0910 N的Ad-0910G)单独使用及联合使用时在小鼠中赋予的免疫保护作用。

结果

与单独施用Ad-0910G相比,Ad-0910G和Ad-0910 N联合使用可增强对颅内攻击的免疫力。表达完整G蛋白的Ad-0910G病毒比表达去除跨膜和胞质结构域的截短G蛋白的Ad-0910Gsped更具免疫原性。此外,使用病毒组合进行口服疫苗接种可带来完全保护。

结论

我们的结果表明,这种病毒组合是一种可行的新型肌肉注射和口服疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/152d/5483267/815b09e533fd/12985_2017_789_Fig1_HTML.jpg

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