Safety and Immunogenicity of Inactivated Varicella-Zoster Virus Vaccine in Adults With Autoimmune Disease: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background. Immunogenicity and safety of inactivated zoster vaccine (ZV(IN)) were evaluated in adults with autoimmune disease. Methods. Adults with autoimmune disease treated with immunosuppressive therapy (biologic or nonbiologic) were randomized to receive 4 doses of ZV(IN), ZV(IN) containing a higher quantity of antigen, or placebo. To measure varicella-zoster virus (VZV)-specific immune responses using glycoprotein enzyme-linked immunosorbent assay (gpELISA) and interferon-gamma enzyme-linked immunospot (IFN-gamma ELISPOT), blood samples were collected at baseline, post-doses 2, 3, and 4. The primary hypothesis was that ZV(IN) would elicit significant VZV-specific immune responses, measured by gpELISA or ELISPOT, at approximately 28 days post-dose 4. Safety and tolerability was assessed through 28 days post-dose 4. Results. ZV(IN) elicited a statistically significant VZV-specific immune response approximately 28 days post-dose 4, measured by gpELISA (estimated geometric mean fold rise from baseline [GMFR] = 1.6 [95% confidence interval [CI], 1.4,1.7], P value <.0001) and IFN-gamma ELISPOT (estimated GMFR = 2.0 [95% CI, 1.6,2.6], P value <.0001); both results met the prespecified success criterion. Overall, 57% (164/289) of all ZV(IN) and 21% (13/62) of placebo recipients reported >= 1 injection-site adverse events (AEs), and 52% (149/289) and 47% (29/62) reported >= 1 systemic AEs, respectively. Eight ZV(IN) and 1 placebo recipients experienced serious AEs, including 2 events (ZV(IN) group) determined by the investigator to be vaccine related (keratitis; amnesia). Overall frequency of AEs decreased with subsequent doses of vaccine. Conclusions. In adults with autoimmune disease, ZV(IN) was well tolerated and elicited statistically significant VZV-specific immune responses approximately 28 days post-dose 4, measured by gpELISA and IFN-gamma ELISPOT.