Seasonal split influenza vaccine induced IgE sensitization against influenza vaccine

Vaccine. 2015 Nov 9;33(45):6099-105. doi: 10.1016/j.vaccine.2015.05.106. Epub 2015 Jul 15.


Although anaphylaxis is an extremely rare vaccine-associated adverse event, it occurred in young children following administration of the 2011/12 seasonal split influenza vaccine, which contained 2-phenoxyethanol as the preservative. These children had high levels of IgE antibodies against influenza vaccine components. We herein investigated why these children were sensitized. One hundred and seventeen series of serum samples were obtained immediately before, and one month after the first and second immunizations with the HA split vaccine of 2011/12. Forty-two sequential serum samples were collected in the acute and convalescent phases (2 and 4 weeks) after natural infection with H1N1 Pdm in 2009. IgE antibodies developed following the vaccination of young children with seasonal split vaccines, whereas no significant IgE response was observed following natural infection with H1N1 Pdm 2009. The prevalence of IgE antibodies was not influenced by outbreaks of H1N1 Pdm. Repeated immunization with the HA split vaccine induced IgE sensitization against the influenza vaccine irrespective of the H1N1, H3N2, or B influenza subtypes. The reasons why anaphylaxis only occurred in recipients of the influenza vaccine containing 2-phenoxyethanol are still being investigated, and the size distribution of antigen particles may have shifted to a slightly larger size. Since the fundamental reason was IgE sensitization, current split formulation for the seasonal influenza vaccine needs to be reconsidered to prevent the induction of IgE sensitization.

Keywords: Anaphylaxis; IgE antibody; IgG4 antibody; Influenza vaccine; Split vaccine.

MeSH terms

  • Adolescent
  • Anaphylaxis / etiology*
  • Child
  • Child, Preschool
  • Disease Outbreaks
  • Ethylene Glycols
  • Female
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunity, Innate
  • Immunoglobulin E / blood*
  • Immunoglobulin E / immunology*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Infant
  • Infant, Newborn
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza B virus / immunology
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control
  • Male
  • Preservatives, Pharmaceutical
  • Seasons
  • Vaccination
  • Vaccines, Inactivated / adverse effects
  • Vaccines, Inactivated / immunology


  • Ethylene Glycols
  • Immunoglobulin G
  • Influenza Vaccines
  • Preservatives, Pharmaceutical
  • Vaccines, Inactivated
  • Immunoglobulin E
  • phenoxyethanol