1818. Immunogenicity of Inactivated Varicella Zoster Vaccine (ZVIN) in Autologous Hematopoietic Stem Cell Transplant (auto-HSCT) Recipients
Session: Oral Abstract Session: Miscellaneous Advances in Vaccinology
Saturday, October 7, 2017: 10:45 AM
Room: 07AB
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 to 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 & 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.

Michael Boeckh, MD, PhD, FIDSA1, Ann Arvin, MD, FIDSA, FPIDS2, Kathleen Mullane, DO, FIDSA3, Drew J. Winston, MD4, Janice (Wes) Brown, MD5, Steven Pergam, MD, MPH, FIDSA1, Kimberly Hurtado, BS6, Lei Pang, PhD6, Ingi Lee, MD, MSCE7, Zoran Popmihajlov, MD, MS6 and on behalf of the V212 Protocol 001 Study Team, (1)Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, (2)Div of ID/Dept of Ped, Stanford University School of Medicine, Stanford, CA, (3)Medicine, University of Chicago Medicine, Chicago, IL, (4)University of California at Los Angeles Medical Center, Los Angeles, CA, (5)Division of Blood and Marrow Transplant and Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Stanford, CA, (6)Merck & Co., Inc., Kenilworth, NJ, (7)Merck & Co., Inc., North Wales, PA

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

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