Evaluation Methods for the Immunogenicity of Varicella and Zoster Vaccines

Abstract

Varicella vaccine has been included in the national immunization program for children since 2005 and zoster vaccine has been released since 2012 in Korea. Even though both varicella and zoster are caused by varicella-zoster virus (VZV), pathogeneses are different. In varicella, neutralizing antibody is very important to protect disease because VZV spreads via blood or lymph. In contrast, cell-mediated immunity is more important in zoster because of the neuronal spread of VZV. Therefore, the measurement methods of the immunogenicity against varicella and zoster vaccines are different. Fluorescent antibody to membrane antigen (FAMA) assay is the gold standard method to detect the protective antibody against VZV. It is still used as a reference test for the other methods. However, the fastidious nature required to perform the FAMA assay limits its use as a routine assay for the evaluation of vaccine immunogenicity. Nowadays, glycoprotein ELISA (gpEIA) is used as an alternative method for FAMA assay. However, there is no agreement over the protective level of gpEIA antibody titer with WHO standard international unit. The immunogenicity of zoster vaccine has been evaluated by responder cell frequency assay and IFN-γ ELISpot assay. Nevertheless, skin test is considered to be a more accurate biomarker for cell-mediated immunity against zoster. For the evaluation of varicella vaccine, it is necessary to standardize the FAMA assay and to set the cut-off value for the gpEIA antibody titer through long-term follow-up study. For zoster vaccine, the evaluation of cell-mediated immunity in Korean adults is urgently needed.