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

Clin Infect Dis. 2017 Oct 1;65(7):1174-1182. doi: 10.1093/cid/cix484.

Abstract

Background: Immunogenicity and safety of inactivated zoster vaccine (ZVIN) 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 ZVIN, ZVIN 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-γ ELISPOT), blood samples were collected at baseline, post-doses 2, 3, and 4. The primary hypothesis was that ZVIN 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: ZVIN 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-γ 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 ZVIN 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 ZVIN and 1 placebo recipients experienced serious AEs, including 2 events (ZVIN 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, ZVIN was well tolerated and elicited statistically significant VZV-specific immune responses approximately 28 days post-dose 4, measured by gpELISA and IFN-γ ELISPOT.

Clinical trials registration: NCT01527383.

Keywords: immunogenicity; inactivated herpes zoster vaccine; safety; tolerability; zoster vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / immunology
  • Autoimmune Diseases / complications*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / virology
  • Double-Blind Method
  • Herpes Zoster / immunology
  • Herpes Zoster / prevention & control*
  • Herpes Zoster Vaccine / adverse effects
  • Herpes Zoster Vaccine / immunology
  • Herpes Zoster Vaccine / therapeutic use*
  • Herpesvirus 3, Human / immunology*
  • Humans
  • Male
  • Middle Aged
  • Vaccines, Inactivated / adverse effects
  • Vaccines, Inactivated / immunology
  • Vaccines, Inactivated / therapeutic use
  • Young Adult

Substances

  • Antibodies, Viral
  • Herpes Zoster Vaccine
  • Vaccines, Inactivated

Associated data

  • ClinicalTrials.gov/NCT01527383