Development of antibody-dependent cellular cytotoxicity in response to recombinant and live-attenuated herpes zoster vaccines

Abstract

Zoster vaccines generate antibody responses against varicella-zoster virus (VZV). We compared antibody-dependent cell cytotoxicity (ADCC) elicited by zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). ADCC mediated by antibodies against VZV lysate (VZV-ADCC) and recombinant glycoprotein E (gE-ADCC) was measured using plasma from 20 RZV- and 20 ZVL-recipients, including half 50–60-years-old and half ≥70-years-old. Solid phase-bound anti-VZV antibodies stimulated TNFα in NK cells as measured by flow cytometry or ELISA. VZV-ADCC pre- and post-immunization was higher in younger vaccinees. ZVL did not appreciably increase VZV-ADCC, whereas RZV increased VZV-ADCC in older vaccinees. ELISA-measured gE-ADCC was similar across groups pre-immunization; significantly increased after ZVL; and RZV and was higher in younger RZV than ZVL recipients. IgG3 antibodies increased after RZV and ZVL, with greater anti-gE than anti-VZV responses. Moreover, gE-ADCC strongly correlated with anti-gE antibody avidity, but there were no appreciable correlations between VZV-ADCC and avidity. NK cells stimulated by anti-gE antibodies showed increased IFNγ and CD107a expression, which was not observed with anti-VZV antibodies. In conclusion, anti-gE antibodies generated more robust ADCC than anti-VZV antibodies. RZV induced higher ADCC antibodies than ZVL depending on the antigen and age of vaccinees. Older adults had lower ADCC antibodies before and after vaccination than younger adults.