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遗传因素和疫苗接种前血液转录组对猪肺炎支原体疫苗接种后抗体水平变异性的影响。

Influence of genetics and the pre-vaccination blood transcriptome on the variability of antibody levels after vaccination against Mycoplasma hyopneumoniae in pigs.

机构信息

Université Paris-Saclay, INRAE, AgroParisTech, GABI, 78350, Jouy-en-Josas, France.

INRAE, GenESI, 17700, Surgères, France.

出版信息

Genet Sel Evol. 2021 Mar 18;53(1):24. doi: 10.1186/s12711-021-00614-5.

Abstract

BACKGROUND

The impact of individual genetic and genomic variations on immune responses is an emerging lever investigated in vaccination strategies. In our study, we used genetic and pre-vaccination blood transcriptomic data to study vaccine effectiveness in pigs.

RESULTS

A cohort of 182 Large White pigs was vaccinated against Mycoplasma hyopneumoniae (M. hyo) at weaning (28 days of age), with a booster 21 days later. Vaccine response was assessed by measuring seric M. hyo antibodies (Ab) at 0 (vaccination day), 21 (booster day), 28, 35, and 118 days post-vaccination (dpv). Inter-individual variability of M. hyo Ab levels was observed at all time points and the corresponding heritabilities ranged from 0.46 to 0.57. Ab persistence was higher in females than in males. Genome-wide association studies with a 658 K SNP panel revealed two genomic regions associated with variations of M. hyo Ab levels at 21 dpv at positions where immunity-related genes have been mapped, DAB2IP on chromosome 1, and ASAP1, CYRIB and GSDMC on chromosome 4. We studied covariations of Ab responses with the pre-vaccination blood transcriptome obtained by RNA-Seq for a subset of 82 pigs. Weighted gene correlation network and differential expression analyses between pigs that differed in Ab responses highlighted biological functions that were enriched in heme biosynthesis and platelet activation for low response at 21 dpv, innate antiviral immunity and dendritic cells for high response at 28 and 35 dpv, and cell adhesion and extracellular matrix for high response at 118 dpv. Sparse partial least squares discriminant analysis identified 101 genes that efficiently predicted divergent responders at all time points. We found weak negative correlations of M. hyo Ab levels with body weight traits, which revealed a trade-off that needs to be further explored.

CONCLUSIONS

We confirmed the influence of the host genetics on vaccine effectiveness to M. hyo and provided evidence that the pre-vaccination blood transcriptome co-varies with the Ab response. Our results highlight that both genetic markers and blood biomarkers could be used as potential predictors of vaccine response levels and more studies are required to assess whether they can be exploited in breeding programs.

摘要

背景

个体遗传和基因组变异对免疫反应的影响是疫苗策略中新兴的研究杠杆。在我们的研究中,我们使用遗传和接种前的血液转录组数据来研究猪的疫苗效力。

结果

182 头大白猪在 28 天大(断奶时)接种了支原体肺炎疫苗(M. hyo),21 天后进行了加强免疫。通过在接种日(0 天)、加强日(21 天)、28 天、35 天和接种后 118 天(dpv)测量血清 M. hyo 抗体(Ab)来评估疫苗反应。在所有时间点都观察到个体间 M. hyo Ab 水平的变异性,相应的遗传力范围为 0.46 至 0.57。女性的 Ab 持续时间高于男性。使用 658K SNP 面板进行全基因组关联研究,在与免疫相关基因映射的位置发现了两个与 21 dpv 时 M. hyo Ab 水平变化相关的基因组区域,1 号染色体上的 DAB2IP 和 4 号染色体上的 ASAP1、CYRIB 和 GSDMC。我们研究了在 82 头猪的亚组中通过 RNA-Seq 获得的接种前血液转录组与 Ab 反应的共变。加权基因相关性网络和 Ab 反应不同的猪之间的差异表达分析突出了生物学功能,这些功能在 21 dpv 时的低反应中富集了血红素生物合成和血小板激活,在 28 和 35 dpv 时的高反应中富集了先天抗病毒免疫和树突状细胞,在 118 dpv 时的高反应中富集了细胞粘附和细胞外基质。稀疏偏最小二乘判别分析确定了 101 个基因,这些基因在所有时间点都能有效地预测出不同的反应者。我们发现 M. hyo Ab 水平与体重性状呈弱负相关,这表明存在需要进一步探索的权衡。

结论

我们证实了宿主遗传学对 M. hyo 疫苗效力的影响,并提供了证据表明接种前的血液转录组与 Ab 反应共同变化。我们的研究结果表明,遗传标记和血液生物标志物都可以作为疫苗反应水平的潜在预测因子,需要进一步研究以评估它们是否可以在育种计划中得到利用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a97/7972226/df6efe147547/12711_2021_614_Fig1_HTML.jpg

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