Background/Purpose:

Patients with autoimmune diseases are often immunocompromised, resulting in higher incidence of HZ than in immunocompetent individuals with significant morbidity and occasional mortality from complications associated with reactivation of the varicella-zoster virus (VZV).  This study evaluated the safety and immunogenicity of an inactivated VZV vaccine (ZV_IN) in adults with autoimmune disease.

Methods:

Patients ≥18 years old with autoimmune disease in this double-blind, placebo-controlled, multicenter Phase II study of a 4-dose ZV_IN regimen (~30 days between doses) were randomized to receive either ZV_IN at an antigen (Ag) level similar to previous studies (~180 patients), ZV_IN containing a higher quantity of Ag (~100 patients; excluded from primary immunogenicity analyses), or placebo (~60 patients).  Randomization was stratified by autoimmune treatment: Stratum 1 patients were receiving ≥1 biologic agent, with or without non-biologic therapy; Stratum 2 patients were receiving ≥1 non-biologic therapy, but no biologic agent.

To measure VZV-specific immune responses using glycoprotein enzyme-linked immunosorbent assay (gpELISA) and interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT), blood samples were collected at the following time points: baseline (all patients), postdose 2 (half of the patient population), postdose 3 (other half of the patient population), postdose 4 (all patients).  The primary hypothesis was that ZV_IN would elicit significant VZV-specific immune responses at ~28 days postdose 4; a Hochberg step-up procedure was employed to test the primary hypotheses on both assays.  The geometric mean fold rise (GMFR) and the geometric mean titer (GMT) or geometric mean count (GMC) were also evaluated.  All vaccinated patients were evaluated for adverse events (AE), including VZV-like rashes, through 28 days postdose 4.

Results:

ZV_IN elicited a statistically significant VZV-specific immune response ~28 days postdose 4 in the per-protocol population measured by gpELISA (GMFR = 1.57 [95% CI: 1.44, 1.72], p-value <0.0001) and IFN-γ ELISPOT (GMFR = 2.01 [95% CI: 1.57, 2.58], p-value <0.0001); both meeting the pre-specified success criterion.

Overall, 75% (217/289) of ZV_IN recipients and 53% (33/62) of placebo recipients reported ≥1 AEs; respectively, 57% (164/289) and 21% (13/62) reported ≥1 injection-site AEs, and 52% (149/289) and 47% (29/62) reported ≥1 systemic AEs.  Eight ZV_IN patients (3%) and one placebo patient (2%) experienced serious AEs, including two events (in ZV_IN group) determined by the investigator to be vaccine-related (keratitis, Day 21 postdose 2; amnesia, Day 1 postdose 2).  One patient in the ZV_IN with higher Ag group experienced a fatal serious AE (respiratory distress, Day 24 postdose 4) assessed as not vaccine-related by the investigator.  In general, the frequencies of AEs did not increase with subsequent doses of vaccine. No ZV_IN recipient had a rash PCR-positive for VZV vaccine strain.

Conclusion:

In adults with autoimmune disease, ZV_IN was well-tolerated and elicited statistically significant VZV-specific immune responses ~28 days postdose 4, as measured by gpELISA and IFN-γ ELISPOT.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-immunogenicity-of-inactivated-varicella-zoster-virus-vaccine-in-adults-with-autoimmune-disease/