A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients

Abstract

Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals. This was a phase 1/2, randomized, observer-blind, placebo-controlled study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50 to 70 days earlier. Subjects (N = 121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 μg varicella-zoster virus glycoprotein E (gE) adjuvanted with AS01B, 3 doses of gE adjuvanted with AS01E, 1 dose of saline followed by 2 doses of gE/AS01B, or 3 doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4(+) T cells expressing ≥2 activation markers after induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to 1 year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at www.clinicaltrials.gov as #NCT00920218.

Figure 1

Subject disposition. gE/AS01_B, glycoprotein E/liposome-based adjuvant (50 µg MPL, 50 µg QS21); gE/AS01_E, glycoprotein E/liposome-based adjuvant (25 µg MPL, 25 µg QS21); SAEs, serious adverse events. *Four subjects (2 in the gE/AS01_E and 2 in the saline groups) with confirmed HZ were included in the safety analysis but were excluded from the immunogenicity analyses at month 15.

Figure 2

Antiglycoprotein E humoral and cell-mediated immune response rates. Shown are the percentages of subjects with humoral (A) and cell-mediated (B) immune responses against VZV glycoprotein E. A humoral response was defined as a greater than or equal to fourfold increase in GMC in subjects who were seropositive before vaccination or a GMC ≥4 times the cutoff value in subjects seronegative before vaccination. A cell-mediated immune response was defined as a greater than or equal to twofold increase in CD4(2⁺) T-cell frequency over prevaccination. Bars indicate means, and errors bars indicate 95% confidence intervals. gE/AS01_B indicates glycoprotein E/liposome-based adjuvant (50 µg MPL, 50 µg QS21); and gE/AS01_E, glycoprotein E/liposome-based adjuvant (25 µg MPL, 25 µg QS21).