Evaluation of varicella zoster virus-specific cell-mediated immunity by using an interferon-γ enzyme-linked immunosorbent assay

• Published in: Journal of immunological methods 2015-11, Vol.426, p.50-55
• Main Authors: Hayashida, Kazumi, Ozaki, Takao, Nishimura, Naoko, Gotoh, Kensei, Funahashi, Keiji, Nakane, Kazumasa, Gomi, Yasuyuki, Manabe, Sadao, Ishikawa, Toyokazu, Yamanishi, Koichi
• Format: Article
• Language: English
• Subjects: Antibodies, Viral - blood; Breakthrough varicella; Cell-mediated immunity; Chickenpox Vaccine - immunology; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Herpesvirus 3, Human - immunology; Humans; IFN-γ ELISA; Immunity, Cellular - immunology; Infant; Interferon-gamma - immunology; Leukocytes, Mononuclear - immunology; Male; Seroconversion; Vaccination; Vaccines, Attenuated - immunology; Varicella vaccine
• ISSN: 0022-1759; 1872-7905
• DOI: 10.1016/j.jim.2015.07.011

Administration of the varicella vaccine induces both varicella-zoster virus (VZV)-specific humoral and cell-mediated immunity (CMI). 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. 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. 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. 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. •We developed a sensitive, quantitative IFN-γ ELISA for evaluating VZV-CMI.•We compared pre- and post-VZV vaccination CMI in 30 healthy children.•92.6% of the subjects showed seroconversion, but half failed to acquire CMI.•2 subjects with post-negative CMI contracted BV despite sufficient VZV antibodies.•CMI is likely related to protection against BV.