Immunogenicity of Inactivated Varicella Zoster Vaccine in Autologous Hematopoietic Stem Cell Transplant Recipients and Patients With Solid or Hematologic Cancer

Michael J Boeckh, Ann M Arvin, Kathleen M Mullane, Luis H Camacho, Drew J Winston, Vicki A Morrison, Kimberly Hurtado, Jessie Durrand Hall, Lei Pang, Shu-Chih Su, Susan S Kaplan, Paula W Annunziato, Zoran Popmihajlov, V212 Protocol 001 Trial Group and V212 Protocol 011 Trial Group, Michael J Boeckh, Ann M Arvin, Kathleen M Mullane, Luis H Camacho, Drew J Winston, Vicki A Morrison, Kimberly Hurtado, Jessie Durrand Hall, Lei Pang, Shu-Chih Su, Susan S Kaplan, Paula W Annunziato, Zoran Popmihajlov, V212 Protocol 001 Trial Group and V212 Protocol 011 Trial Group

Abstract

Background: In phase 3 trials, inactivated varicella zoster virus (VZV) vaccine (ZVIN) was well tolerated and efficacious against herpes zoster (HZ) in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and patients with solid tumor malignancies receiving chemotherapy (STMc) but did not reduce HZ incidence in patients with hematologic malignancies (HMs). Here, we describe ZVIN immunogenicity from these studies.

Methods: Patients were randomized to ZVIN or placebo (4 doses). Immunogenicity was assessed by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and VZV interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in patients receiving all 4 doses without developing HZ at the time of blood sampling.

Results: Estimated geometric mean fold rise ratios (ZVIN/placebo) by gpELISA and IFN-y ELISPOT ~28 days post-dose 4 were 2.02 (95% confidence interval [CI], 1.53-2.67) and 5.41 (95% CI, 3.60-8.12) in auto-HSCT recipients; 1.88 (95% CI, 1.79-1.98) and 2.10 (95% CI, 1.69-2.62) in patients with STMc; and not assessed and 2.35 (95% CI, 1.81-3.05) in patients with HM.

Conclusions: ZVIN immunogenicity was directionally consistent with clinical efficacy in auto-HSCT recipients and patients with STMc even though HZ protection and VZV immunity were not statistically correlated. Despite a lack of clinical efficacy in patients with HM, ZVIN immunogenicity was observed in this population. Immunological results did not predict vaccine efficacy in these 3 populations.

Clinical trial registration: NCT01229267, NCT01254630.

Keywords: cell-mediated immunity; humoral immunity; immunocompromised adults; immunogenicity; inactivated zoster vaccine.

© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
VZV-specific antibody observed response by gpELISA in auto-HSCT recipients and patients with STMc (per-protocol population). Abbreviations: auto-HSCT, autologous hematopoietic stem cell transplant; gpELISA, glycoprotein enzyme-linked immunosorbent assay; STMc, solid tumor malignancies receiving chemotherapy; ZVIN, inactivated varicella zoster.
Figure 2.
Figure 2.
VZV-specific cell-mediated observed immune response by interferon (IFN)-γ ELISPOT assay in auto-HSCT recipients, patients with STMc, and patients with HM (per-protocol population). Abbreviations: auto-HSCT, autologous hematopoietic stem cell transplant; GMC, geometric mean count; HM, hematologic malignancies; IFN-γ ELISPOT, IFN-γ enzyme-linked immunospot; PBMCs, peripheral blood mononuclear cells; STMc, solid tumor malignancies receiving chemotherapy; ZVIN, inactivated varicella zoster.

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