Integrative genomic analysis of the human immune response to influenza vaccination.
Integrative genomic analysis of the human immune response to influenza vaccination.
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DOI：
10.7554/elife.00299
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发表时间：
2013-07-16
期刊：
影响因子：
7.7
通讯作者：
Shaw CA
中科院分区：
文献类型：
--
作者：
Franco LM;Bucasas KL;Wells JM;Niño D;Wang X;Zapata GE;Arden N;Renwick A;Yu P;Quarles JM;Bray MS;Couch RB;Belmont JW;Shaw CA
鉴定导致疫苗反应性变化的宿主遗传因素可能揭示影响疫苗效力的重要机制。我们在接种季节性流感疫苗的人群中进行了一项综合性、纵向研究，结合了遗传学、转录和免疫学数据。我们确定了20个基因表现出对疫苗接种的转录反应，基因表达的显着基因型效应，以及转录和抗体反应之间的相关性。结果表明，参与膜运输和抗原加工的基因水平的变化显着影响人类对流感疫苗接种的反应。更广泛地说，我们证明了一个综合性的研究设计是一个有效的替代现有的方法来识别复杂性状的基因。http://dx.doi.org/10.7554/eLife.00299.001疫苗通过激发免疫系统对特定病毒或微生物作出反应来增强对疾病的抵抗力。通过向免疫系统呈现弱化（或死亡）形式的病原体或其毒素或表面蛋白，疫苗触发针对病毒或微生物的抗体的产生。如果接种疫苗的个体遇到病原体，他们的免疫系统应该能够识别并摧毁它。许多疫苗还包括一种辅助剂，称为佐剂，以进一步刺激免疫反应。流感是一种RNA病毒，通常被称为“流感”，是一种影响鸟类和哺乳动物的传染病。每年发生季节性流行病，影响2-7%的人口。根据世界卫生组织的数据，流感每年导致近500万人住院，并导致多达50万人死亡。接种疫苗是预防季节性流感的主要策略，但对疫苗的反应差异很大，部分原因是个体的基因组成或基因型的差异。然而，基因如何影响对疫苗接种的反应以及对流感的易感性的细节仍然不清楚。为了研究健康成人对季节性流感疫苗免疫应答变异的遗传基础，Franco等人将个体基因型信息与其基因转录和疫苗接种抗体应答的测量结果相结合。他们确定了20个有助于对疫苗产生不同免疫反应的基因。这些蛋白质中几乎有一半编码与免疫系统无关的蛋白质，但在膜运输和细胞内运输等过程中具有更普遍的作用。关注这些基因可能使研究人员能够发现那些不太可能对疫苗产生反应的人。它还可以为疫苗开发开辟新的研究途径：研究人员应该开发针对这20个基因编码的蛋白质的佐剂，而不是设计针对已知免疫机制的佐剂。DOI：http://dx.doi.org/10.7554/eLife.00299.002网站
Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI: http://dx.doi.org/10.7554/eLife.00299.001 Vaccines increase resistance to disease by priming the immune system to respond to specific viruses or microorganisms. By presenting a weakened (or dead) form of a pathogen, or its toxins or surface proteins, to the immune system, vaccines trigger the production of antibodies against the virus or microorganism. If a vaccinated individual then encounters the pathogen, their immune system should be able to recognize and destroy it. Many vaccines also include a secondary agent, known as an adjuvant, to further stimulate the immune response. Influenza, an RNA virus commonly referred to as the ‘flu’, is an infectious disease that affects both birds and mammals. Seasonal epidemics occur each year affecting 2–7% of the population. According to the World Health Organization, influenza leads to nearly 5 million hospitalizations each year and causes up to half a million deaths. Vaccination is a primary strategy for the prevention of seasonal influenza, but responses to the vaccine vary markedly, partly because of variation in the genetic makeup or genotype of individuals. However, the details of how genes influence response to vaccination, and indeed susceptibility to influenza, remain unclear. To investigate the genetic basis of variation in the immune response of healthy adults to the seasonal influenza vaccine, Franco et al. combined information about the genotypes of individuals with measurements of their gene transcription and antibody response to vaccination. They identified 20 genes that contributed to differential immune responses to the vaccine. Almost half of these encode proteins that are not specifically associated with the immune system, but have more general roles in processes such as membrane trafficking and intracellular transport. Focusing on these genes may enable researchers to spot those individuals who are less likely to respond to a vaccine. It could also open up new avenues of research for vaccine development: rather than designing adjuvants that target known immune mechanisms, researchers should develop adjuvants that target the proteins encoded by these 20 genes. DOI: http://dx.doi.org/10.7554/eLife.00299.002