Systems Biology of Vaccination for Seasonal Influenza in Humans

Nat Immunol. 2011 Jul 10;12(8):786-95. doi: 10.1038/ni.2067.

Abstract

Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.

Publication types

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

MeSH terms

  • Adaptive Immunity / immunology
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Viral / blood
  • Gene Expression Profiling
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunity, Innate / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Orthomyxoviridae / immunology*
  • Seasons
  • Systems Biology / methods
  • Vaccination / methods
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology
  • Young Adult

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Attenuated
  • Vaccines, Inactivated

Associated data

  • GEO/GSE29619