Immunogenicity of Inactivated Varicella Zoster Vaccine (ZV(IN)) in Autologous Hematopoietic Stem Cell Transplant (auto-HSCT) Recipients

BACKGROUND: Recipients of auto-HSCT have an increased risk of herpes zoster (HZ) infection; however, live attenuated varicella-zoster virus (VZV) vaccine is contraindicated in these patients. In this pivotal Phase III study (V212-001; NCT01229267) inactivated VZV vaccine (ZV(IN)) reduced the rate of HZ infection compared with placebo (estimated vaccine efficacy, 63.8%) and was well tolerated. Immunogenicity of ZV(IN)in recipients of auto-HSCT was assessed in the Phase III study as an exploratory objective. METHODS: Adults undergoing auto-HSCT were randomized to receive either ZV(IN)(n = 560) or placebo (n = 564), administered in a 4-dose regimen. Doses 1 through 4 were administered ~30 days before and ~30, ~60, and ~90 days following auto-HSCT. VZV-specific immune responses were measured at Day 1, ~28 days post-vaccinations 3 and 4, and annually until the end of the study. VZV-specific antibody responses were measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) in all patients; cell-mediated immune responses were measured by VZV interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay in a randomized subset of patients (n = 403). RESULTS: Geometric mean titers (GMT) were significantly higher and the ratios of the gpELISA and IFN-γ ELISPOT were significantly greater in the ZV(IN)group compared with the placebo group (Tables 1 and 2). CONCLUSION: ZV(IN) elicited higher VZV-specific humoral and cell-mediated responses in adult auto-HSCT recipients when compared with placebo ~28 days and ~1 year post-dose 4. These results indicate that ZV(IN) is immunogenic in these patients who are ineligible for live attenuated HZ vaccine, which is consistent with previously observed clinical efficacy. DISCLOSURES: M. Boeckh, Merck: Investigator, Research Contractor and Scientific Advisor, Consulting fee and Research support; GlaxoSmithKline: Research Contractor, Research support; A. Arvin, Merck: Scientific Advisor, Consulting fee; K. Mullane, Merck: Scientific Advisor, Grant recipient; D. J. Winston, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; J. Brown, Merck: Clinical adjudication and site investigator and Investigator, Consulting fee; Cellerant Therapeutics: Consultant, Cellerant developing and executing clinical trials of myeloid progenitor cells in neutropenia for which I hold the patent; S. Pergam, Merck: Consultant and Investigator, Consulting fee; K. Hurtado, Merck: Employee and Shareholder, Salary; L. Pang, Merck: Employee and Shareholder, Salary; I. Lee, Merck: Employee, Salary; Z. Popmihajlov, Merck & Co., Inc.: Employee and Shareholder, Salary