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额外插入 gC 基因可增强 TK/gI/gE 缺失伪狂犬病病毒在小鼠中的免疫效力。

Additional Insertion of gC Gene Triggers Better Immune Efficacy of TK/gI/gE-Deleted Pseudorabies Virus in Mice.

机构信息

Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

出版信息

Viruses. 2024 Apr 29;16(5):706. doi: 10.3390/v16050706.

DOI:10.3390/v16050706
PMID:38793591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11125823/
Abstract

In recent years, pseudorabies virus (PRV) variants have resulted in an epidemic in swine herds and huge economic losses in China. Therefore, it is essential to develop an efficacious vaccine against the spread of PRV variants. Here, the triple-gene-deletion virus and the triple-gene-deletion plus gC virus were constructed by homologous recombination (HR). And then, their growth capacity, proliferation ability, and immune efficacy were evaluated. The results showed that the growth kinetics of the recombinant viruses were similar to those of the parental strain PRV-AH. Compared with the triple-gene-deletion virus group, the more dominant level of neutralizing antibody (NA) can be induced in the triple-gene-deletion plus gC virus group with the same 10 TCID dose after 4 and 6 weeks post-initial immunization (PII) ( < 0.0001). In addition, the antibody titers in mice immunized with the triple-gene-deletion plus gC virus were significantly higher than those immunized with triple-gene deletion virus with the same 10 TCID dose after 6 weeks PII ( < 0.001). More importantly, in the triple-gene-deletion plus gC virus group with 10 TCID, the level of NA was close to that in the triple-gene deletion virus group with 10 TCID at 6 weeks PII. Meanwhile, the cytokines IL-4 and IFN-γ in sera were tested by enzyme-linked immunosorbent assay (ELISA) in each group. The highest level of IL-4 or IFN-γ was also elicited in the triple-gene deletion plus gC virus group at a dose of 10 TCID. After challenge with PRV-AH, the survival rates of the triple-gene deletion plus gC virus immunized groups were higher than those of other groups. In immunized groups with 10 TCID, the survival rate shows a significant difference between the triple-gene deletion plus gC virus group (75%, 6/8) and the triple-gene deletion virus group (12.5%, 1/8). In general, the immune efficacy of the PRV TK/gI/gE-deleted virus can be increased with additional gC insertion in mice, which has potential for developing an attenuated vaccine candidate for PRV control.

摘要

近年来,伪狂犬病病毒(PRV)变异株在中国的猪群中引发了疫情,并造成了巨大的经济损失。因此,开发一种有效的疫苗来控制 PRV 变异株的传播至关重要。本研究通过同源重组(HR)构建了三基因缺失病毒和三基因缺失加 gC 病毒,并评估了它们的生长能力、增殖能力和免疫效果。结果表明,重组病毒的生长动力学与亲本 PRV-AH 株相似。与三基因缺失病毒组相比,在相同的 10TCID 剂量下,三基因缺失加 gC 病毒组在初次免疫后 4 周和 6 周时可以诱导更高水平的中和抗体(NA)(<0.0001)。此外,在初次免疫后 6 周时,用相同剂量的 10TCID 免疫的三基因缺失加 gC 病毒组的抗体滴度明显高于用三基因缺失病毒免疫的小鼠(<0.001)。更重要的是,在 10TCID 的三基因缺失加 gC 病毒组中,NA 水平接近 6 周时用 10TCID 的三基因缺失病毒组。同时,通过酶联免疫吸附试验(ELISA)检测各组血清中的细胞因子 IL-4 和 IFN-γ。在 10TCID 剂量下,三基因缺失加 gC 病毒组也能诱导最高水平的 IL-4 或 IFN-γ。用 PRV-AH 攻毒后,三基因缺失加 gC 病毒免疫组的存活率均高于其他组。在 10TCID 免疫组中,三基因缺失加 gC 病毒组(75%,6/8)与三基因缺失病毒组(12.5%,1/8)的存活率有显著差异。总之,在小鼠中,PRV TK/gI/gE 缺失病毒的免疫效果可以通过额外插入 gC 来提高,这为开发 PRV 控制的减毒疫苗候选株提供了潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/b9eed4b2cfbd/viruses-16-00706-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/f4a5a90902d2/viruses-16-00706-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/d55da4e8cc4d/viruses-16-00706-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/b9eed4b2cfbd/viruses-16-00706-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/6f3d250e559a/viruses-16-00706-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/1c14601f354a/viruses-16-00706-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/01535ba5416b/viruses-16-00706-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/32303c4466ba/viruses-16-00706-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/06308c0198c8/viruses-16-00706-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/e5661b1f880c/viruses-16-00706-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/ecac84ddc1b7/viruses-16-00706-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/f4a5a90902d2/viruses-16-00706-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/d55da4e8cc4d/viruses-16-00706-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d4/11125823/b9eed4b2cfbd/viruses-16-00706-g010.jpg

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