Proteomics Core: Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity

蛋白质组学核心：识别新生儿疫苗免疫原性生物标志物的系统生物学

基本信息

批准号：
10063824
负责人：
Hanno Steen
金额：
$ 11.64万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-27 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063824
关键词：
Achievement Address Adjuvant Adult Age Attenuated Australia BCG Live BCG Vaccine Bioinformatics Biological Markers Biological Models Birth Blood Blood specimen Boston Childhood Clinical Collaborations Data Development Ensure Future Gambia Gene Expression Profile Geography Goals Growth Healthcare Hepatitis B Vaccines Human Immune Immune system Immunization Immunization Programs Immunology Immunophenotyping Impairment In Vitro Individual Infant Infection Institutes International Isotope Labeling Laboratories Leukocytes Life Maps Measures Medical Research Methods Modeling Modern Medicine Molecular Molecular Profiling National Institute of Allergy and Infectious Disease Neonatal New Guinea Newborn Infant Outcome Papua New Guinea Participant Pediatric Hospitals Phase Phenotype Plasma Population Protein Translation Pathway Proteins Proteome Proteomics Risk Sampling Services Site Systems Biology Techniques Time United States National Institutes of Health Vaccine Adjuvant Vaccine Design Vaccines Validation adaptive immune response aluminum sulfate base biomarker identification biomarker signature candidate marker cohort data integration data management immunogenicity in vitro Model in vivo innovation insight interest liquid chromatography mass spectrometry neonatal immunity novel novel vaccines proteomic signature response success synergism transcriptome transcriptomics vaccine development vaccine response vaccinology

项目摘要

PROJECT SUMMARY Despite the undeniable success of immunization, >2 million infants still die annually from infections. Birth is the most reliable point of healthcare contact and is thus an ideal time point to ensure widespread immunization. However, neonatal immunity is distinct from adult as it is attenuated after birth, such that neonatal vaccine responses are often impaired. In this context, there is an urgent need to develop new neonatal vaccines, to date a slow, risky and error-prone undertaking. To provide the molecular basis for such efforts and accelerate and de-risk future vaccine development, the NIAID/NIH has initiated the Human Immunology Project Consortium with a focus on applying unbiased, global molecular (OMIC) and immunophenotyping techniques to interrogate the human immune system and its response to challenges such as immunization. One objective of our proposal on systems biology for the identification of biomarkers of neonatal vaccine immunogenicity is to map changes in neonatal plasma and leukocyte proteomes across the first 7 days of life in response to immunization with (a) nothing – i.e., delayed immunization to Day 7 to define ontogeny (change with age), (b) Hepatitis B vaccine (HBV) for which there is a clear correlate of protection, (c) Bacille Calmette-Guérin (BCG) vaccine, known to modify HBV action, or (d) (HBV + BCG). Additional data are generated by employing novel in vitro immunization platforms employing blood from the same study participants (Project 3). The proteome basal state and landscape changes will be correlated with changes in the transcriptome (Service Core 1) and immune phenotype/status (Project 2). Integrative bioinformatic analysis in Project 1 will identify basal and vaccine-induced patterns of gene expression, protein translation, and pathways associated with successful immunization. HIPC Core/Project data will be shared/analyzed via a robust Data Management Core. To support these efforts, the Proteomics Core will pursue the following Specific Aims, using samples collected in The Gambia (Clinical Core (CC)-Site 1) and Papa New Guinea (CC-Site 2), and/or generated in the Levy Laboratory at Boston Children's Hospital (Project 3): Specific Aim1: Characterize the basal, ontogenic and vaccine-induced state of the neonatal plasma proteome across the first 7 days of life. Specific Aim2: Characterize the basal, ontogenic and vaccine-induced leukocyte proteome from the same blood sample as the plasma samples. Specific Aim3. Validate HBV-induced proteomic signatures correlating with immunogenicity using targeted LC/MS Approaches on samples from validation cohorts at CC Sites 1 and -2. Overall our Proteomics Core will provide groundbreaking insight into vaccine-induced plasma and leukocyte proteome signatures that correlate with protection thereby informing future neonatal vaccine development.

项目摘要尽管免疫取得了不可否认的成功，但> 200万婴儿仍死于感染。出生是医疗保健接触的最可靠点，因此是确保宽度免疫接种的理想时间点。然而，新生儿免疫与成人不同，因为它在出生后被减弱，因此新生儿疫苗反应通常会受到损害。在这种情况下，迫切需要开发新的新生疫苗约会缓慢，风险且容易出错。为这种努力提供分子基础并加速 NIAID/NIH发起了人类免疫学项目，以及脱离风险的未来疫苗开发财团着重于应用无偏的全球分子（OMIC）和免疫表型技术询问人类免疫系统及其对免疫化等挑战的反应。一个目标我们关于系统生物学的建议，以鉴定新生儿疫苗免疫原性的生物标志物是在生命的前7天，新生儿血浆和白细胞蛋白质组织的地图变化是响应的没有（a）没有的免疫 - 即延迟免疫到第7天，以定义个体发育（随着年龄的变化），（b）肝炎B疫苗（HBV）为其具有明显的保护相关性，（c）巴奇·塞莱特·戈林（BCG）已知可以修改HBV作用的疫苗，或（D）（HBV + BCG）。通过使用小说来生成其他数据从同一研究参与者中使用血液的体外免疫平台（项目3）。蛋白质组基本状态和景观变化将与转录组（服务核心1）和免疫表型/状态（项目2）。项目1中的综合生物信息学分析将确定基本和疫苗诱导的基因表达模式，蛋白质翻译和与成功相关的途径免疫。 HIPC核心/项目数据将通过强大的数据管理核心共享/分析。为了支持这些努力，蛋白质组学核心将使用收集的样本追求以下特定目标在冈比亚（临床核心（CC） - 站点1）和爸爸新几内亚（CC-Site 2）和/或在征费中产生波士顿儿童医院的实验室（项目3）：特定目标1：表征新生儿血浆蛋白质组的基本，个体基础和疫苗诱导的状态在生命的前7天。特定AIM2：表征来自同一的基本，个体基因和疫苗诱导的白细胞蛋白质组作为血浆样品的血液样本。特定的AIM3。使用靶向的验证HBV诱导的蛋白质组学特征与免疫原性相关 LC/MS在CC位点1和-2的验证队列中的样品接近。总体而言，我们的蛋白质组学核心将为疫苗诱导的血浆和白细胞提供开创性的见解与保护相关的蛋白质组特征，从而为未来的新生儿疫苗开发提供了信息。