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基于猪痘病毒载体的疫苗:皮下刺种接种后的减毒和生物安全性评估。

Swinepox virus vector-based vaccines: attenuation and biosafety assessments following subcutaneous prick inoculation.

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

College of Veterinary Sciences, Fujian Agricultural and Forestry University, Fuzhou, China.

出版信息

Vet Res. 2018 Feb 7;49(1):14. doi: 10.1186/s13567-018-0510-5.

Abstract

Swinepox virus (SPV) has several advantages as a potential clinical vector for a live vector vaccine. In this study, to obtain a safer and more efficient SPV vector, three SPV mutants, Δ003, Δ010, and ΔTK were successfully constructed. A virus replication experiment showed that these SPV mutants had lower replication abilities compared to wtSPV in 10 different host-derived cell lines. Animal experiments with mouse and rabbit models demonstrate that these three mutants and wtSPV did not cause any clinical signs of dermatitis. No fatalities were observed during a peritoneal challenge assay with these mutants and wtSPV in a mouse model. Additionally, the three mutants and wtSPV were not infectious at 60 h after vaccination in rabbit models. Furthermore, we evaluated biosafety, immunogenicity and effectiveness of the three mutants in 65 1-month-old piglets. The results show that there were no clinical signs of dermatitis in the Δ003 and ΔTK vaccination groups. However, mild signs were observed in the Δ010 vaccination groups when virus titres were high, and apparent clinical signs were observed at the sites of inoculation. Samples from all experimental pig groups were assessed by qPCR, and no SPV genomic DNA was found in five organs, faeces or blood. This suggests that the infectious abilities of wtSPV and the SPV mutants were poor and limited. In summary, this study indicates that two mutants of SPV, Δ003 and ΔTK, may be promising candidates for an attenuated viral vector in veterinary medicine.

摘要

猪痘病毒(SPV)作为活载体疫苗的潜在临床载体具有多种优势。在本研究中,为了获得更安全、更有效的 SPV 载体,成功构建了三种 SPV 突变体,Δ003、Δ010 和 ΔTK。病毒复制实验表明,与 wtSPV 相比,这三种 SPV 突变体在 10 种不同的宿主来源细胞系中的复制能力较低。小鼠和兔模型的动物实验表明,这三种突变体和 wtSPV 均未引起任何皮炎临床症状。在小鼠模型的腹膜攻毒试验中,这三种突变体和 wtSPV 均未引起死亡。此外,在兔模型中,接种后 60 小时,这三种突变体和 wtSPV 均无感染性。此外,我们评估了三种突变体和 wtSPV 在 65 头 1 月龄仔猪中的生物安全性、免疫原性和有效性。结果表明,Δ003 和 ΔTK 接种组无皮炎临床症状。然而,当病毒滴度较高时,Δ010 接种组出现轻度症状,且接种部位出现明显的临床症状。通过 qPCR 评估所有实验猪组的样本,在五个器官、粪便或血液中均未发现 SPV 基因组 DNA。这表明 wtSPV 和 SPV 突变体的感染能力较差且有限。综上所述,本研究表明,SPV 的两种突变体Δ003 和 ΔTK 可能是兽医领域有希望的减毒病毒载体候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bee5/5804073/759c424ee628/13567_2018_510_Fig1_HTML.jpg

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