Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults

被引:13
作者
Ben-Othman, Rym [1 ,2 ]
Cai, Bing [1 ]
Liu, Aaron C. [1 ]
Varankovich, Natallia [1 ]
He, Daniel [1 ]
Blimkie, Travis M. [3 ]
Lee, Amy H. [4 ]
Gill, Erin E. [3 ]
Novotny, Mark [5 ]
Aevermann, Brian [5 ]
Drissler, Sibyl [6 ]
Shannon, Casey P. [7 ,8 ]
McCann, Sarah [1 ]
Marty, Kim [1 ]
Bjornson, Gordean [1 ]
Edgar, Rachel D. [9 ]
Lin, David Tse Shen [9 ]
Gladish, Nicole [9 ]
Maclsaac, Julia [9 ]
Amenyogbe, Nelly [2 ]
Chan, Queenie [10 ]
Llibre, Alba [11 ]
Collin, Joyce [12 ]
Landais, Elise [12 ,13 ]
Le, Khoa [12 ,13 ]
Reiss, Samantha M. [14 ]
Koff, Wayne C. [15 ]
Havenar-Daughton, Colin [14 ]
Heran, Manraj [16 ]
Sangha, Bippan [16 ]
Walt, David [17 ]
Krajden, Mel [18 ]
Crotty, Shane [14 ]
Sok, Devin [12 ,13 ]
Briney, Bryan [12 ]
Burton, Dennis R. [12 ]
Duffy, Darragh [11 ]
Foster, Leonard J. [10 ]
Mohn, William W. [19 ]
Kobor, Michael S. [9 ]
Tebbutt, Scott J. [7 ,8 ,20 ]
Brinkman, Ryan R. [6 ,21 ]
Scheuermann, Richard H. [5 ,14 ]
Hancock, Robert E. W. [3 ]
Kollmann, Tobias R. [1 ,2 ]
Sadarangani, Manish [1 ]
机构
[1] BC Childrens Hosp, Vaccine Evaluat Ctr, Res Inst, Vancouver, BC, Canada
[2] Univ Western Australia, Telethon Kids Inst, Nedlands, WA, Australia
[3] Univ British Columbia, Ctr Microbial Dis & Immun Res, Vancouver, BC, Canada
[4] Simon Fraser Univ, Burnaby, BC, Canada
[5] J Craig Venter Inst La Jolla, Dept Informat, La Jolla, CA USA
[6] Terry Fox Lab, Vancouver, BC, Canada
[7] St Pauls Hosp, Prevent Organ Failure PROOF Ctr Excellence, Vancouver, BC, Canada
[8] St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada
[9] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC, Canada
[10] Univ British Columbia, Dept Biochem & Mol Biol, Fac Med, Vancouver, BC, Canada
[11] Inst Pasteur, Translat Immunol Lab, Paris, France
[12] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA
[13] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA
[14] La Jolla Inst Immunol LJI, Ctr Infect Dis & Vaccine Res, La Jolla, CA USA
[15] Human Vaccines Project, New York, NY USA
[16] BC Childrens Hosp, Dept Radiol, Vancouver, BC, Canada
[17] Harvard Univ, Brigham & Womens Hosp, Harvard Med Sch, Wyss Inst,Dept Pathol, Boston, MA 02115 USA
[18] British Columbia Ctr Dis Control, Vancouver, BC, Canada
[19] Univ British Columbia, Life Sci Inst, Dept Microbiol & Immunol, Vancouver, BC, Canada
[20] Univ British Columbia, Div Resp Med, Dept Med, Vancouver, BC, Canada
[21] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada
关键词
multi-omic; single cell; lymph node; gene expression; bio-informatic; immunimonitoring; vaccine; NEUTRALIZING ANTIBODY-RESPONSES; RNA-SEQ; HIGH-THROUGHPUT; ULTRASENSITIVE DETECTION; QUALITY-CONTROL; SINGLE NUCLEI; CELL;
D O I
10.3389/fimmu.2020.580373
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 similar to 350 mL of blood, 12 microbiome samples, and lymph node fine needle aspirates obtained over a similar to 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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页数:15
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