Reduced varicella-zoster-virus (VZV)-specific lymphocytes and IgG antibody avidity in solid organ transplant recipients

Abstract

Background: Varicella-zoster-virus (VZV) infection may cause significant morbidity and mortality in immunocompromised patients. So far, only IgG-anti-VZV antibody concentrations were used to estimate immunity against VZV, but the antibody binding strength (avidity) together with VZV-specific cellular responses have not been evaluated in solid organ transplant (SOT) recipients.

Methods: Thus, we assessed the humoral and cellular immune responses to two doses of the VZV vaccine (vacc) and wild-type VZV infection (wt) in 23 kidney (KTx) and 19 liver transplant (LTx) recipients including children and adults compared to 48 healthy controls (HC) for measurement of IgG-anti-VZV relative avidity index (RAI) and frequency of VZV-specific peripheral blood mononuclear cells (PBMCs) in vaccinated individuals using an adapted ELISA and IFN-gamma ELISPOT, respectively.

Results: KTx(wt) (median RAI 72.3%) or LTx(wt) (79.2%) and KTx(vacc) (91.0%) or LTx(vacc) (72.5%) showed lower avidities compared to HC(wt) (84.5%) and HC(vacc) (94.0%), respectively, despite equally distributed IgG-anti-VZV concentrations. RAI>60% (high avidity) was detected in all HC, but only in 69.0% of SOT patients. KTx(vacc) (median 64 spot forming units SFU/500,000 PBMCs) and LTx(vacc) (67 SFU) had significantly lower VZV-specific cellular responses compared to HC(vacc) (268 SFU).

Conclusions: The diminished cellular reactivity to VZV has to be considered in SOT patients receiving immunosuppressive treatments when evaluating immunity against VZV. IgG antibody avidity and VZV-specific cellular responses may serve as additional markers to evaluate immunity against VZV in SOT recipients. The role of wild-type exposures and endogenous VZV re-activation on long-term immunity in SOT patients has to be awaited to establish recommendations for vaccine spacing in these patients, considering immunogenicity and safety aspects.