AUTHOR=Ben-Othman Rym , Cai Bing , Liu Aaron C. , Varankovich Natallia , He Daniel , Blimkie Travis M. , Lee Amy H. , Gill Erin E. , Novotny Mark , Aevermann Brian , Drissler Sibyl , Shannon Casey P. , McCann Sarah , Marty Kim , Bjornson Gordean , Edgar Rachel D. , Lin David Tse Shen , Gladish Nicole , Maclsaac Julia , Amenyogbe Nelly , Chan Queenie , Llibre Alba , Collin Joyce , Landais Elise , Le Khoa , Reiss Samantha M. , Koff Wayne C. , Havenar-Daughton Colin , Heran Manraj , Sangha Bippan , Walt David , Krajden Mel , Crotty Shane , Sok Devin , Briney Bryan , Burton Dennis R. , Duffy Darragh , Foster Leonard J. , Mohn William W. , Kobor Michael S. , Tebbutt Scott J. , Brinkman Ryan R. , Scheuermann Richard H. , Hancock Robert E. W. , Kollmann Tobias R. , Sadarangani Manish TITLE=Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.580373 DOI=10.3389/fimmu.2020.580373 ISSN=1664-3224 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.