title: Seasonal split influenza vaccine induced IgE sensitization against influenza vaccine.
abstract: 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.
authors.affiliation: Kitasato Institute for Life Sciences, Laboratory of Viral Infection, Tokyo, Japan. Electronic address: tetsuo-n@lisci.kitasato-u.ac.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Kumagai Pediatric Clinic, Sapporo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Konan Kosei Hospital, Department of Pediatrics, Konan, Aichi Prefecture, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Nishimura
authors.affiliation: Konan Kosei Hospital, Department of Pediatrics, Konan, Aichi Prefecture, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Okafuji Pediatric Clinic, Himeji, Hyogo Prefecture, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okafuji
authors.affiliation: Suzuki Pediatric Clinic, Ube, Yamaguchi Prefecture, Japan.
authors.forename: Eitaro
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Saiwai Pediatric Clinic, Tachikawa, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Miyata
authors.affiliation: Fukuoka Dental College, Division of Oral & Medical Management, Department of Medicine, Section of Pediatrics, Fukuoka, Fukuoka Prefecture, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okada
authors.affiliation: National Mie Hospital, Department of Pediatrics, Tsu, Mie Prefecture, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ihara
mesh_terms: D000293:Adolescent; D000707:Anaphylaxis / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D005026:Ethylene Glycols; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D011310:Preservatives, Pharmaceutical; D012621:Seasons; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology
chemical_list: D005026:Ethylene Glycols; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011310:Preservatives, Pharmaceutical; D015164:Vaccines, Inactivated; D007073:Immunoglobulin E; C005398:phenoxyethanol
keywords: Anaphylaxis; IgE antibody; IgG4 antibody; Influenza vaccine; Split vaccine