LAUSR

Abstract 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 (ZVIN) reduced the rate of HZ infection compared with placebo (estimated vaccine efficacy, 63.8%) and was well tolerated. Immunogenicity of ZVINin 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 ZVIN(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 ZVINgroup compared with the placebo group (Tables 1 and 2). Table 1. GMT 28 days post-dose 4 (PD4) Vaccine Placebo gpELISA n = 102 n = 108 241.8 (95% CI: 186.2, 313.9) 105.8 (95% CI: 84.6, 132.3) IFN-γ ELISPOT n = 102 n = 116 62.8 (95% CI: 45.8, 86.2) 10.4 (95% CI: 7.9, 13.7) Table 2. Ratios of geometric mean fold rise between the vaccine and placebo groups (ZVIN/placebo) gpELISA (n = 764) IFN-γ ELISPOT (n = 339) Pre-vaccination and 28 days 
PD4 1.79 (95% CI: 1.39, 2.32) 5.41 (95% CI: 3.60, 8.12) Pre-vaccination and 1 year 
PD4 1.30 (95% CI: 0.99, 1.71) 4.12 (95% CI: 2.62, 6.47) Conclusion ZVIN 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 ZVIN 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