title: Evaluation of varicella zoster virus-specific cell-mediated immunity by using an interferon-γ enzyme-linked immunosorbent assay.
abstract: BACKGROUND
  Administration of the varicella vaccine induces both varicella-zoster virus (VZV)-specific humoral and cell-mediated immunity (CMI).
  
  
  OBJECTIVE
  To assess VZV-CMI, we developed an interferon γ enzyme-linked immunosorbent assay (IFN-γ ELISA) that measures the quantity of total IFN-γ in culture supernatants of human peripheral blood mononuclear cells.
  
  
  METHODS
  We evaluated this method by comparing the pre- and post-vaccination immune response in peripheral blood mononuclear cells of 30 healthy children who were administered an initial varicella vaccination at Konan Kosei hospital.
  
  
  RESULTS
  IFN-γ ELISA showed well-validated results; CMI was not detectable pre-immunization but became detectable post-immunization. Seroconversion was detected in 92.6% of subjects by the immune adherence hemagglutination test; however, half of the subjects did not display an increase in CMI levels. We also compared the incidence of breakthrough varicella and herpes zoster development between CMI post-positive and post-negative vaccinees at 1-2years after the last VZV vaccination. Eight subjects had a history of varicella or herpes zoster exposure post-VZV vaccination. Two of them with post-negative CMI contracted breakthrough varicella 15-16months after the last vaccination, even though they had sufficient VZV-specific antibody levels to be considered seropositive and seroprotected. Conversely, the others with post-positive CMI did not contract breakthrough varicella, despite experiencing extensive VZV exposure through casual contact with playmates and family.
  
  
  CONCLUSIONS
  The CMI data generated by this IFN-γ ELISA may accurately reflect real-world immune status, and CMI may be closely related to immunoprotection against breakthrough varicella development.
authors.affiliation: The Research Foundation for Microbial Diseases of Osaka University, 3-1, Yamada-Oka, Suita, Osaka, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Hayashida
authors.affiliation: Department of Pediatrics, Konan Kosei Hospital, 137 Ohmatsubara, Takaya-cho, Konan, Aichi Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Department of Pediatrics, Konan Kosei Hospital, 137 Ohmatsubara, Takaya-cho, Konan, Aichi Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Nishimura
authors.affiliation: Department of Pediatrics, Konan Kosei Hospital, 137 Ohmatsubara, Takaya-cho, Konan, Aichi Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Gotoh
authors.affiliation: Department of Clinical Laboratory, Konan Kosei Hospital, 137 Ohmatsubara, Takaya-cho, Konan, Aichi, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Funahashi
authors.affiliation: Department of Clinical Laboratory, Konan Kosei Hospital, 137 Ohmatsubara, Takaya-cho, Konan, Aichi, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Nakane
authors.affiliation: Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, 4-1-70, Seto-cho, Kanonji, Kagawa, Japan. Electronic address: ygomi@mail.biken.or.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gomi
authors.affiliation: Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, 4-1-70, Seto-cho, Kanonji, Kagawa, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Manabe
authors.affiliation: Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, 4-1-70, Seto-cho, Kanonji, Kagawa, Japan.
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: The Research Foundation for Microbial Diseases of Osaka University, 3-1, Yamada-Oka, Suita, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamanishi
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D019433:Chickenpox Vaccine / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D000069078:Seroconversion; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019433:Chickenpox Vaccine; D014613:Vaccines, Attenuated; D007371:Interferon-gamma
keywords: Breakthrough varicella; Cell-mediated immunity; IFN-γ ELISA; Varicella vaccine