|
- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults
Rym Ben-Othman 1 2 , Bing Cai 1 , Aaron C Liu 1 , Natallia Varankovich 1 , Daniel He 1 , Travis M Blimkie 3 , Amy H Lee 4 , Erin E Gill 3 , Mark Novotny 5 , Brian Aevermann 5 , Sibyl Drissler 6 , Casey P Shannon 7 , Sarah McCann 1 , Kim Marty 1 , Gordean Bjornson 1 , Rachel D Edgar 8 , David Tse Shen Lin 8 , Nicole Gladish 8 , Julia Maclsaac 8 , Nelly Amenyogbe 2 , Queenie Chan 9 , Alba Llibre 10 , Joyce Collin 11 , Elise Landais 11 12 , Khoa Le 11 12 , Samantha M Reiss 13 , Wayne C Koff 14 , Colin Havenar-Daughton 13 , Manraj Heran 15 , Bippan Sangha 15 , David Walt 16 , Mel Krajden 17 , Shane Crotty 13 , Devin Sok 11 12 , Bryan Briney 11 , Dennis R Burton 11 , Darragh Duffy 10 , Leonard J Foster 9 , William W Mohn 18 , Michael S Kobor 8 , Scott J Tebbutt 7 19 , Ryan R Brinkman 6 20 , Richard H Scheuermann 5 13 , Robert E W Hancock 3 , Tobias R Kollmann 1 2 , Manish Sadarangani 1
Affiliations
Affiliations
1
Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada.
2
Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.
3
Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
4
Simon Fraser University, Burnaby, BC, Canada.
5
Department of Informatics, J. Craig Venter Institute (La Jolla), La Jolla, CA, United States.
6
Terry Fox Laboratory, Vancouver, BC, Canada.
7
Prevention of Organ Failure (PROOF) Centre of Excellence and Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada.
8
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
9
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
10
Translational Immunology Lab, Institut Pasteur, Paris, France.
11
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States.
12
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, United States.
13
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States.
14
Human Vaccines Project, New York, NY, United States.
15
Department of Radiology, BC Children's Hospital, Vancouver, BC, Canada.
16
Wyss Institute at Harvard University, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
17
British Columbia Centre for Disease Control, Vancouver, BC, Canada.
18
Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
19
Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada.
20
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
PMID: 33250895 PMCID: PMC7672042 DOI: 10.3389/fimmu.2020.580373
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.
Keywords: bio-informatic; gene expression; immunimonitoring; lymph node; multi-omic; single cell; vaccine.
Copyright © 2020 Ben-Othman, Cai, Liu, Varankovich, He, Blimkie, Lee, Gill, Novotny, Aevermann, Drissler, Shannon, McCann, Marty, Bjornson, Edgar, Lin, Gladish, Maclsaac, Amenyogbe, Chan, Llibre, Collin, Landais, Le, Reiss, Koff, Havenar-Daughton, Heran, Sangha, Walt, Krajden, Crotty, Sok, Briney, Burton, Duffy, Foster, Mohn, Kobor, Tebbutt, Brinkman, Scheuermann, Hancock, Kollmann and Sadarangani. |
|
发表于 2020-12-1 08:45