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

Frontiers in Pediatrics

article

Olubukola T. Idoko¹  Rym Ben-Othman⁵  Oludare A. Odumade²  Kerry McEnaney²  Nelly Amenyogbe⁸  William S. Pomat⁹  Simon van Haren²  Guzmán Sanchez-Schmitz²  Ryan R. Brinkman^1,11  Hanno Steen²  Robert E. W. Hancock^1,14  Kinga K. Smolen²  Scott J. Tebbutt^1,15  Peter C. Richmond⁸  Anita H. J. van den Biggelaar⁸  Tobias R. Kollmann⁸  Ofer Levy²  Al Ozonoff²  Beate Kampmann¹  Oghenebrume Wariri¹  Abdulazeez Imam¹  Casey P. Shannon^1,15  Tida Dibassey¹  Joann Diray-Arce²  Alansana Darboe¹  Julia Strandmark¹ 

[1] Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine;Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, United States;CIH LMU Center for International Health, Medical Center of the University of Munich (LMU);The Vaccine Centre, London School of Hygiene and Tropical Medicine, United Kingdom;Department of Pediatrics, BC Children's Hospital, University of British Columbia;Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital, United States;Department of Cardiology, Boston Children's Hospital, United States;Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia;Papua New Guinea Institute of Medical Research;Harvard Medical School, United States;BC Cancer Agency;Department of Medical Genetics, University of British Columbia;Department of Pathology, Boston Children's Hospital, United States;Department of Microbiology & Immunology, University of British Columbia;PROOF Centre of Excellence;Centre for Heart Lung Innovation, University of British Columbia;Division of Respiratory Medicine, Department of Medicine;Division of Pediatrics, School of Medicine, Perth Children's Hospital, University of Western Australia;Broad Institute of MIT & Harvard, United States

关键词: markers;    newborn;    vaccine;    immunogenicity;    systems biology;    OMICS;   

DOI  :  10.3389/fped.2020.00197

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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 ~ 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 ~ 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.

【 授权许可】

CC BY