Metabolites as biomarkers of adverse reactions following vaccination: A pilot study using nuclear magnetic resonance metabolomics

Vaccine. 2017 Mar 1;35(9):1238-1245. doi: 10.1016/j.vaccine.2017.01.056. Epub 2017 Feb 3.


An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers.

Keywords: Adverse Events Following Immunizations (AEFI); Immunizations; Metabolomics; Myocarditis; Subclinical myocarditis; Vaccinations.

Publication types

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

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Asymptomatic Diseases
  • Biomarkers / blood*
  • Drug-Related Side Effects and Adverse Reactions / blood
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Metabolomics*
  • Myocarditis / blood
  • Myocarditis / diagnosis
  • Pericarditis / blood
  • Pericarditis / diagnosis
  • Pilot Projects
  • Smallpox Vaccine / administration & dosage
  • Smallpox Vaccine / adverse effects
  • Troponin / blood
  • Vaccination / adverse effects
  • Vaccines / adverse effects*


  • Biomarkers
  • Smallpox Vaccine
  • Troponin
  • Vaccines