Frontiers in Immunology (Nov 2020)
Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults
- Rym Ben-Othman,
- Rym Ben-Othman,
- Bing Cai,
- Aaron C. Liu,
- Natallia Varankovich,
- Daniel He,
- Travis M. Blimkie,
- Amy H. Lee,
- Erin E. Gill,
- Mark Novotny,
- Brian Aevermann,
- Sibyl Drissler,
- Casey P. Shannon,
- Sarah McCann,
- Kim Marty,
- Gordean Bjornson,
- Rachel D. Edgar,
- David Tse Shen Lin,
- Nicole Gladish,
- Julia Maclsaac,
- Nelly Amenyogbe,
- Queenie Chan,
- Alba Llibre,
- Joyce Collin,
- Elise Landais,
- Elise Landais,
- Khoa Le,
- Khoa Le,
- Samantha M. Reiss,
- Wayne C. Koff,
- Colin Havenar-Daughton,
- Manraj Heran,
- Bippan Sangha,
- David Walt,
- Mel Krajden,
- Shane Crotty,
- Devin Sok,
- Devin Sok,
- Bryan Briney,
- Dennis R. Burton,
- Darragh Duffy,
- Leonard J. Foster,
- William W. Mohn,
- Michael S. Kobor,
- Scott J. Tebbutt,
- Scott J. Tebbutt,
- Ryan R. Brinkman,
- Ryan R. Brinkman,
- Richard H. Scheuermann,
- Richard H. Scheuermann,
- Robert E. W. Hancock,
- Tobias R. Kollmann,
- Tobias R. Kollmann,
- Manish Sadarangani
Affiliations
- Rym Ben-Othman
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Rym Ben-Othman
- Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia
- Bing Cai
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Aaron C. Liu
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Natallia Varankovich
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Daniel He
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Travis M. Blimkie
- Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada
- Amy H. Lee
- Simon Fraser University, Burnaby, BC, Canada
- Erin E. Gill
- Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada
- Mark Novotny
- Department of Informatics, J. Craig Venter Institute (La Jolla), La Jolla, CA, United States
- Brian Aevermann
- Department of Informatics, J. Craig Venter Institute (La Jolla), La Jolla, CA, United States
- Sibyl Drissler
- Terry Fox Laboratory, Vancouver, BC, Canada
- Casey P. Shannon
- Prevention of Organ Failure (PROOF) Centre of Excellence and Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada
- Sarah McCann
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Kim Marty
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Gordean Bjornson
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Rachel D. Edgar
- Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- David Tse Shen Lin
- Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Nicole Gladish
- Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Julia Maclsaac
- Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Nelly Amenyogbe
- Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia
- Queenie Chan
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Alba Llibre
- 0Translational Immunology Lab, Institut Pasteur, Paris, France
- Joyce Collin
- 1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Elise Landais
- 1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Elise Landais
- 2IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, United States
- Khoa Le
- 1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Khoa Le
- 2IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, United States
- Samantha M. Reiss
- 3Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- Wayne C. Koff
- 4Human Vaccines Project, New York, NY, United States
- Colin Havenar-Daughton
- 3Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- Manraj Heran
- 5Department of Radiology, BC Children’s Hospital, Vancouver, BC, Canada
- Bippan Sangha
- 5Department of Radiology, BC Children’s Hospital, Vancouver, BC, Canada
- David Walt
- 6Wyss Institute at Harvard University, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Mel Krajden
- 7British Columbia Centre for Disease Control, Vancouver, BC, Canada
- Shane Crotty
- 3Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- Devin Sok
- 1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Devin Sok
- 2IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, United States
- Bryan Briney
- 1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Dennis R. Burton
- 1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Darragh Duffy
- 0Translational Immunology Lab, Institut Pasteur, Paris, France
- Leonard J. Foster
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- William W. Mohn
- 8Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
- Michael S. Kobor
- Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Scott J. Tebbutt
- Prevention of Organ Failure (PROOF) Centre of Excellence and Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada
- Scott J. Tebbutt
- 9Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada
- Ryan R. Brinkman
- Terry Fox Laboratory, Vancouver, BC, Canada
- Ryan R. Brinkman
- 0Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Richard H. Scheuermann
- Department of Informatics, J. Craig Venter Institute (La Jolla), La Jolla, CA, United States
- Richard H. Scheuermann
- 3Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- Robert E. W. Hancock
- Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada
- Tobias R. Kollmann
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- Tobias R. Kollmann
- Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia
- Manish Sadarangani
- Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, BC, Canada
- DOI
- https://doi.org/10.3389/fimmu.2020.580373
- Journal volume & issue
-
Vol. 11
Abstract
Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling. Methods that support this intensive sampling need to be developed and validated as feasible. To this end, we describe here a detailed approach that was applied in a study of 15 healthy adults, who were immunized with hepatitis B vaccine. Sampling included ~350 mL of blood, 12 microbiome samples, and lymph node fine needle aspirates obtained over a ~7-month period, enabling comprehensive analysis of the immune response at the molecular level, including single cell and tissue sample analysis. Samples were collected for analysis of immune phenotyping, whole blood and single cell gene expression, proteomics, lipidomics, epigenetics, whole blood response to key immune stimuli, cytokine responses, in vitro T cell responses, antibody repertoire analysis and the microbiome. Data integration was undertaken using different approaches—NetworkAnalyst and DIABLO. Our results demonstrate that such intensive sampling studies are feasible in healthy adults, and data integration tools exist to analyze the vast amount of data generated from a multi-omics systems biology approach. This will provide the basis for a better understanding of vaccine-induced immunity and accelerate future rational vaccine design.
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