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. 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. 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.

中文翻译：

---

遗传学和接种前血液转录组对猪接种猪肺炎支原体后抗体水平变异性的影响

个体遗传和基因组变异对免疫反应的影响是疫苗接种策略中研究的一个新兴杠杆。在我们的研究中，我们使用遗传和疫苗接种前的血液转录组数据来研究猪的疫苗有效性。一组 182 头大白猪在断奶时（28 日龄）接种了猪肺炎支原体（M.hyo）疫苗，21 天后加强接种。通过在接种后 0（接种日）、21（加强接种日）、28、35 和 118 天（dpv）测量血清 M.hyo 抗体（Ab）来评估疫苗反应。在所有时间点均观察到 M.hyo Ab 水平的个体间变异性，相应的遗传力范围为 0.46 至 0.57。女性的 Ab 持久性高于男性。使用 658 K SNP 面板进行的全基因组关联研究揭示了两个基因组区域与 21 dpv 在免疫相关基因已定位的位置、染色体 1 上的 DAB2IP 和 ASAP1、CYRIB 和 GSDMC 上的变异相关。 4 号染色体。我们研究了通过 RNA-Seq 获得的 82 头猪的接种前血液转录组的 Ab 反应的协变。抗体反应不同的猪之间的加权基因相关网络和差异表达分析突出了富含血红素生物合成和血小板活化的生物学功能，在 21 dpv 时低反应，先天抗病毒免疫和树突细胞在 28 和 35 dpv 时高反应，和细胞粘附和细胞外基质在 118 dpv 时具有高响应。稀疏偏最小二乘判别分析确定了 101 个在所有时间点有效预测不同反应者的基因。我们发现 M.hyo Ab 水平与体重特征之间存在微弱的负相关，这揭示了需要进一步探索的权衡。我们证实了宿主遗传学对 M.hyo 疫苗有效性的影响，并提供了疫苗接种前血液转录组与 Ab 反应共变的证据。我们的结果强调，遗传标记和血液生物标记都可以用作疫苗反应水平的潜在预测因子，需要更多的研究来评估它们是否可以在育种计划中加以利用。这揭示了需要进一步探索的权衡。我们证实了宿主遗传学对 M.hyo 疫苗有效性的影响，并提供了疫苗接种前血液转录组与 Ab 反应共变的证据。我们的结果强调，遗传标记和血液生物标记都可以用作疫苗反应水平的潜在预测因子，需要更多的研究来评估它们是否可以在育种计划中加以利用。这揭示了需要进一步探索的权衡。我们证实了宿主遗传学对 M.hyo 疫苗有效性的影响，并提供了疫苗接种前血液转录组与 Ab 反应共变的证据。我们的结果强调，遗传标记和血液生物标记都可以用作疫苗反应水平的潜在预测因子，需要更多的研究来评估它们是否可以在育种计划中加以利用。