SAN DIEGO, CA—Both formulations of a new adjuvant varicella-zoster virus (VZV) subunit vaccine candidate were immunogenic and well tolerated when tested in adult autologous hematopoietic cell transplant (HCT) recipients, a population for whom the licensed live-attenuated vaccine is not appropriate due to their immunocompromised status, according to a study presented during IDWeek 2012.
The Phase 1/2a randomized, observer-blind, placebo-controlled, multicenter study included adults aged ≥18 years who had multiple myeloma, non-Hodgkin B or T cell lymphoma, Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous HCT within the previous 50–70 days and had had a previous VZV infection, reported Francisco M. Marty, MD, from the Dana-Farber Cancer Institute & Brigham and Women’s Hospital, Boston, MA, and colleagues. Subjects were stratified by hematologic disease group and randomized 1:1:1:1 to receive by intramuscular injection at Months 0, 1, and 3:
- · Three doses of 50μg VZV glycoprotein E (gE) combined with the liposome-based adjuvant AS01B (50μg MPL, 50μg QS21)
- · Three doses of 50μg gE combined with the liposome-based adjuvant AS01E (25μg MPL, 25μg QS21)
- · One dose of saline followed by two doses of gE/AS01B
- · Three doses of saline (placebo group)
A total of 120 participants were vaccinated at 10 study centers. The investigators measured serum anti-gE antibody concentrations by ELISA; the assay cut-off was 18milli-international units/mL. Frequencies of gE-specific CD4+ T cells expressing ≥2 activation markers among interferon-gamma, interleukin-2, tumor necrosis factor-alpha, and CD40 ligand per 106 cells after in vitro stimulation with gE were measured by intracellular cytokine staining followed by flow cytometry.
At 1 month after final dose, anti-gE antibody concentrations and gE-activated CD4+ T cell frequencies were significantly higher with all gE/AS01 regimens than with saline (all P<0.0001). Three doses of gE/AS01B were found to be more immunogenic than two (P<0.05); however, three doses of gE/AS01B were not significantly more immunogenic than three doses of gE/AS01E.
In the 7-day post vaccination period, solicited or unsolicited adverse events (AEs) were reported by 94.3% of vaccine and 68.9% of saline recipients, with 26.1% and 6.6% being Grade 3 AEs, respectively. Pain at the injection site, fatigue, and myalgia were the most commonly reported AEs.
Ten subjects experienced non-fatal serious AEs. Three participants died during the study, all due to progression of multiple myeloma (one subject each in the gE/AS01E 3-dose, gE/AS01B 2-dose and saline groups). There were no vaccination-related serious AEs or deaths. One PCR-confirmed case of herpes zoster occurred in the saline group during the active phase of the study.