Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea
Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea
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DOI：
10.3389/fped.2020.00197
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发表时间：
2020-04-30
影响因子：
2.6
通讯作者：
Kampmann, Beate
中科院分区：
文献类型：
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作者：
Idoko, Olubukola T.;Smolen, Kinga K.;Kampmann, Beate
背景：感染会导致显着的发病率和死亡率，特别是在幼儿和低收入和中等收入国家。虽然疫苗是对抗传染病的一种极具成本效益的工具，但人们对疫苗在早期诱导保护的细胞和分子途径知之甚少。免疫在生命早期是独特的，我们需要更精确地理解生命早期保护机制，以便为新型儿科疫苗的开发提供信息。方法和分析：我们将应用转录组学、蛋白质组学、代谢组学、多重细胞因子/趋化因子、腺苷脱氨酶和流式细胞术免疫细胞表型分析来描绘与疫苗免疫原性相对应的早期细胞和分子特征。该方法将应用于冈比亚的新生儿队列（N 类似于 720）在出生时接受：(1) 单独的乙型肝炎 (HepB) 疫苗，(2) 单独的卡介苗 (BCG) 疫苗，或 (3) HepB 和 BCG 疫苗，(4) HepB 和 BCG 疫苗最迟延迟至第 10 天。每个研究参与者将在 DOL0 时抽取基线外周血样本，并在 DOL1、-3 或 -7 以及较晚的时间点抽取第二份血样，以评估 HepB 疫苗的免疫原性。血液将通过“小样本大数据”标准操作程序进行分级，从而实现多个下游系统生物学检测。我们将应用单变量和多变量框架以及多 OMIC 数据集成来识别与抗乙型肝炎 (抗 HB) 滴度（一种既定的保护相关性）相关的特征。从一部分参与者收集脐带血样本将使人类体外模型能够测试在计算机中确定的有关疫苗作用的机制假设。母亲抗 HB 滴度和婴儿微生物组也将与我们的研究结果相关，这些研究结果将在巴布亚新几内亚的一个较小的队列中得到验证（N 类似于 80）。 伦理与传播：该研究已得到冈比亚政府/MRCG 联合伦理委员会和波士顿儿童医院机构审查委员会的批准。巴布亚新几内亚医学研究咨询委员会正在进行伦理审查。在提交研究成果以供出版后，所有去识别化的数据将上传到公共存储库。将组织反馈会议，向研究社区传播成果。
Background: Infection contributes to significant morbidity and mortality particularly in the very young and in low- and middle-income countries. While vaccines are a highly cost-effective tool against infectious disease little is known regarding the cellular and molecular pathways by which vaccines induce protection at an early age. Immunity is distinct in early life and greater precision is required in our understanding of mechanisms of early life protection to inform development of new pediatric vaccines.Methods and Analysis: We will apply transcriptomic, proteomic, metabolomic, multiplex cytokine/chemokine, adenosine deaminase, and flow cytometry immune cell phenotyping to delineate early cellular and molecular signatures that correspond to vaccine immunogenicity. This approach will be applied to a neonatal cohort in The Gambia (N similar to 720) receiving at birth: (1) Hepatitis B (HepB) vaccine alone, (2) Bacille Calmette Guerin (BCG) vaccine alone, or (3) HepB and BCG vaccines, (4) HepB and BCG vaccines delayed till day 10 at the latest. Each study participant will have a baseline peripheral blood sample drawn at DOL0 and a second blood sample at DOL1,-3, or-7 as well as late timepoints to assess HepB vaccine immunogenicity. Blood will be fractionated via a "small sample big data" standard operating procedure that enables multiple downstream systems biology assays. We will apply both univariate and multivariate frameworks and multi-OMIC data integration to identify features associated with anti-Hepatitis B (anti-HB) titer, an established correlate of protection. Cord blood sample collection from a subset of participants will enable human in vitro modeling to test mechanistic hypotheses identified in silico regarding vaccine action. Maternal anti-HB titer and the infant microbiome will also be correlated with our findings which will be validated in a smaller cohort in Papua New Guinea (N similar to 80).Ethics and Dissemination: The study has been approved by The Gambia Government/MRCG Joint Ethics Committee and The Boston Children's Hospital Institutional Review Board. Ethics review is ongoing with the Papua New Guinea Medical Research Advisory Committee. All de-identified data will be uploaded to public repositories following submission of study output for publication. Feedback meetings will be organized to disseminate output to the study communities.