Kim Ha-Hyun, Yang Dong-Kun, Nah Jin-Ju, Song Jae-Young, Cho In-Soo
Viral Disease Division, Animal and Plant Quarantine Agency, Gimcheon, 39660, MAFRA, Republic of Korea.
Virol J. 2017 Jun 24;14(1):122. doi: 10.1186/s12985-017-0789-2.
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.
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.
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.
Our results suggest that this combination of viruses is a viable new intramuscular and oral vaccine candidate.
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。
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。
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。
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。