Evaluating varicella-zoster virus vaccine immunogenicity through Fc-mediated antibody functions: the roles of ADCP and ADCC

Abstract

Assessing the functional activity of vaccine-induced antibodies is critical for evaluating immunogenicity. We developed and validated antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) assays to quantify Fc-mediated antibody responses elicited by varicella and zoster vaccines. Both assays demonstrated robust performance and broad linearity. Antibody titers were measured using fluorescent antibody to membrane antigen (FAMA) and ELISA. ADCP and ADCC activities, along with FAMA and ELISA geometric mean titers (GMTs), were significantly increased in post- versus pre-vaccination sera (p < 0.0001). Strong correlations were observed between ADCP and ADCC activities and both FAMA and ELISA GMTs. Although children exhibited lower total varicella-zoster virus-specific IgG levels than adults, higher IgG3 subclass levels in children were associated with comparable Fc-mediated activities. These results highlight the utility of ADCP and ADCC as valuable assays for evaluating Fc-mediated antibody function and as potential surrogates of protective immunity to varicella and zoster vaccination. © The Author(s) 2026.