表达犬GM-CSF的重组狂犬病病毒是一种有效的犬用口服狂犬病疫苗。

Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

作者信息

Zhou Ming, Wang Lei, Zhou Songqin, Wang Zhao, Ruan Juncheng, Tang Lijun, Jia Ziming, Cui Min, Zhao Ling, Fu Zhen F

机构信息

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Academy of Preventive Medicine, Wuhan, China.

出版信息

Oncotarget. 2015 Nov 17;6(36):38504-16. doi: 10.18632/oncotarget.5904.

Abstract

Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.

摘要

开发有效的口服狂犬病疫苗是提高流浪狗免疫覆盖率的重要一步,因为流浪狗无法进行肠胃外疫苗接种。我们之前的研究表明,表达细胞因子/趋化因子的重组狂犬病病毒(RABV)通过招募和激活树突状细胞(DCs)和B细胞,在小鼠口服免疫后诱导强大的保护性免疫反应。为了开发一种有效的犬用口服狂犬病疫苗,构建了一种表达犬GM-CSF的重组减毒RABV,命名为LBNSE-dGM-CSF,并用于犬模型的口服疫苗接种。口服LBNSE-dGM-CSF疫苗的犬外周血中激活的DCs或B细胞明显多于接种亲本病毒LBNSE的犬,特别是在免疫后3天(dpi)。结果,用LBNSE-dGM-CSF免疫的犬检测到的病毒中和抗体(VNA)水平明显高于用亲本病毒免疫的犬。所有免疫犬均受到4500 MICLD50野生型RABV SXTYD01致死性攻击的保护。通过巢式RT-PCR和免疫组织化学检测发现,口服疫苗接种后LBNSE-dGM-CSF主要在扁桃体中复制。综上所述,我们的结果表明,LBNSE-dGM-CSF可能是一种有前景的犬用口服狂犬病疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7fd/4770717/a415b6f87d55/oncotarget-06-38504-g001.jpg

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