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.

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

“…Increased age is also associated with increased baseline abundance of pro-inflammatory agalactosylated and asialylated IgG ( 300 , 309 , 335 , 376 ) which may contribute to generation of dampened or uncoordinated Fc effector functions upon vaccination. Overall, these antibody impairments likely underpin the decreased FcγR binding and Fc effector functions observed in elderly individuals ( 37 , 388 ).…”

“…Intriguingly, low IgG4 levels, similar to that observed in RV144 vaccinees, were observed after only two doses of VAX003, suggesting that repeated protein boosting may have contributed to skewed IgG4 subclass profile ( 82 ). On the other hand, the zoster vaccine, consisting of two doses of adjuvanted recombinant glycoprotein E elicited improved ADCC against herpes zoster compared to the live virus vaccine ( 388 ). This suggests that muted functional responses are not necessarily inherent to recombinant protein vaccine platforms and are likely also influenced by number of doses.…”

Varicella Zoster Virus-Specific Hyperimmunoglobulin in the Adjuvant Treatment of Immunocompromised Herpes Zoster Patients: A Case Series

“…In general, immunity to VZV is thought to be driven by T-cells particularly in the maintenance of latent VZV in a subclinical state. However, when there is a decline in the immune system of the host, which can occur with iatrogenic immune suppression or aging, reactivation of latent virus may occur [ 14 ]. Another component contributing to immunity against VZV appears to be antibody-dependent cellular cytotoxicity (ADCC), since patients with defects in natural killer cells, which are central to ADCC, suffer from severe and recurrent, often fatal VZV infections [ 14 ].…”

“…Virostatic drugs and VZV-IgG have a synergistic mode of action in the treatment of VZV; while the virostatic drug prevents viral replication inside the cell, VZV-specific IgGs mediate ADCC towards infected cells and also neutralize viral particles, thus preventing further dissemination [ 14 – 16 ].…”

Therapeutic vaccines for herpesviruses

“…Both the live-attenuated zoster vaccine (Zostavax) and subunit zoster vaccine (VZV glycoprotein E formulated with AS01b adjuvant, Shingrix) reduce the incidence of zoster ( 6 ). These two vaccines induce virus-specific CD4 + and CD8 + T cell responses to VZV ( 7 ) and antibody that mediates antibody-dependent cellular cytotoxicity (ADCC) ( 8 ), both of which are important for killing virus-infected cells. In addition, VZV glycoprotein E functions as a viral Fc receptor and antibodies against glycoprotein E may block viral Fc receptor activity, resulting in enhanced ADCC.…”