Metabolic Phenotypes of Response to Vaccination in Humans

Cell. 2017 May 18;169(5):862-877.e17. doi: 10.1016/j.cell.2017.04.026. Epub 2017 May 11.


Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.

Keywords: Zostavax; herpes zoster vaccine; immune response; metabolomics; multiscale; shingles; systems biology; transcriptomics.

MeSH terms

  • Adaptive Immunity
  • Adult
  • Aged
  • Aging
  • Antibody Formation
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Herpes Zoster Vaccine / immunology*
  • Humans
  • Inositol Phosphates / immunology
  • Longitudinal Studies
  • Male
  • Metabolomics
  • Middle Aged
  • Sex Characteristics
  • Sterols / metabolism
  • Viral Load


  • Herpes Zoster Vaccine
  • Inositol Phosphates
  • Sterols