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

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical trial registration</jats:title> <jats:p>NCT01229267, NCT01254630.</jats:p> </jats:sec>

Assessing and restoring adaptive immunity to HSV, VZV, and HHV-6 in solid organ and hematopoietic cell transplant recipients

“…SOT and autologous HCT recipients receiving RZV in clinical trials demonstrated similar or slightly reduced humoral and cellular immune responses compared to immunocompetent J o u r n a l P r e -p r o o f adults (20,45,(48)(49)(50)(51)(52). In a placebo-controlled clinical trial of RZV in autologous HCT recipients, vaccine efficacy was ~70% and RZV elicited humoral and cellular responses in 67% and 93% of vaccinees, respectively (48).…”

Cellular Immune Response after Vaccination in Patients with Cancer—Review on Past and Present Experiences

“…This strategy on early vaccination after autologous HCT was further pursued with recombinant VZV subunit or inactivated VZV vaccines [75,[78][79][80]. The ZOE-HSCT randomized, placebo-controlled phase 3 trial demonstrated efficacy of a two-dose regimen of a recombinant VZV vaccine against VZV glycoprotein E administered 50-70 days after autologous HCT against development of HZ [80].…”

“…The V212-001 phase 3 trial evaluated a four-dose regimen of inactivated VZV vaccine administered prior as well as 30, 60, and 90 days after autologous HCT [78]. Cellular response to vaccination, assessed by IFNγ enzyme-linked immunospot assay, showed a ratio of estimated geometric mean fold rise (GMFR) in vaccine versus placebo group of 5.41 at four weeks after dose 4 and 3.32 at two years [79]. Compared to baseline, a GMFR of 1.85 was observed in vaccine recipients at four weeks after dose 4, which increased to 3.32 at two years, while estimated geometric mean count in the placebo group was actually lower at four weeks after dose 4 compared to baseline [79].…”

Herpes zoster prophylaxis with low‐dose acyclovir in patients with malignant lymphoma and multiple myeloma treated with autologous stem cell transplantation

“…Another possibility is the vaccination of patients with a new vaccine which appears to be effective for a proportion of about two thirds of ASCT patients. 9,[16][17][18][19][20] To evaluate the impact of acyclovir prophylaxis, we analyzed our patients treated with ASCT in our institution since 2009, since 2015 combined with low-dose acyclovir prophylaxis (400 mg per day) for 12 months after ASCT.…”