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

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 AmenyogbeQueenie Chan, Alba Llibre, Joyce Collin, Elise Landais, Khoa Le, Samantha M. Reiss, Wayne C. Koff, Colin Havenar-Daughton, Manraj Heran, Bippan Sangha, David Walt, Mel Krajden, Shane Crotty, Devin Sok, Bryan Briney, Dennis R. Burton, Darragh Duffy, Leonard J. Foster, William W. Mohn, Michael S. Kobor, Scott J. Tebbutt, Ryan R. Brinkman, Richard H. Scheuermann, Robert E.W. Hancock, Tobias R. Kollmann, Manish Sadarangani

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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.

Original languageEnglish
Article number580373
JournalFrontiers in Immunology
Volume11
DOIs
Publication statusPublished - 4 Nov 2020

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