Prospective evaluation of recombinant Herpes zoster vaccine in SSc: immunogenicity, safety and disease outcomes.

Abstract

to evaluate humoral immune response to recombinant zoster vaccine(RZV) in immunosuppressed patients with systemic sclerosis(SSc) compared with healthy controls, to identify factors influencing vaccine response, and to assess RZV safety and impact on patient-reported outcome measures(PROMs) and disease activity(DA). A sub-analysis of a randomized, double-blind, placebo-controlled trial included 76 immunosuppressed SSc patients and 304 healthy controls(CG) receiving two RZV doses. SSc patients were randomized to receive two initial doses of RZV or placebo; after unblinding, the placebo group received two doses of RZV. Anti-glycoprotein-E antibodies were measured at baseline and six-weeks post-second dose. Geometric mean concentrations(GMCs) and factor increase(FI) were calculated. Cell-mediated immunogenicity (CMI) was evaluated. DA and PROMs were assessed using standardized instruments. Body mass index(BMI) defined nutritional status. SSc patients(47.4%diffuse/52.6%limited) were younger(53.0 vs 55.0 years, p= 0.002) and had lower BMI(p= 0.005) than CG. Humoral response were significantly lower in SSc compared with controls(92.6% vs 99.7%,p= 0.001). SSc patients showed significantly lower GMC(5.81 vs 12.6, p< 0.001) and FI(31.0 vs 59.4, p< 0.001) than controls, with comparable CMI(p> 0.05). Disease subtypes, demographic factors, immunosuppressive therapies or nutritional status did not predict impaired vaccine response(p> 0.05). Local adverse events were reduced in SSc patients(73.7% vs 86.5%,p= 0.024), while systemic reactions were comparable overall(59.2% vs 61.5%,p= 0.712). DA and PROMs outcomes remained stable(p> 0.05). RZV was well tolerated. Despite the high seroconversion rate, the immune response was significantly lower in magnitude compared with controls, without triggering DA or worsening PROMs. ∼50% lower antibody concentrations in SS raise concerns about long-term protection, underscoring the need for ongoing monitoring. ClinicalTrials.gov; NCT05879419.