Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

Front Immunol. 2020 Nov 30:11:578801. doi: 10.3389/fimmu.2020.578801. eCollection 2020.

Abstract

Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.

Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.

Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.

Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual's immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

Keywords: baseline immunity; hepatitis B vaccination; multi-omic analysis; network analysis; vaccine response.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Epigenesis, Genetic
  • Epigenomics
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Genomics*
  • Hepatitis B / genetics
  • Hepatitis B / metabolism
  • Hepatitis B / microbiology
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / blood
  • Hepatitis B Vaccines / therapeutic use*
  • Humans
  • Immunogenicity, Vaccine*
  • Male
  • Middle Aged
  • Prospective Studies
  • Protein Interaction Maps
  • Proteomics
  • Systems Biology*
  • Time Factors
  • Transcriptome
  • Treatment Outcome
  • Vaccination*

Substances

  • Engerix-B
  • Hepatitis B Antibodies
  • Hepatitis B Vaccines